diff --git a/.github/workflows/wordlist.txt b/.github/workflows/wordlist.txt index e69de29..1fa8d45 100644 --- a/.github/workflows/wordlist.txt +++ b/.github/workflows/wordlist.txt @@ -0,0 +1,15 @@ +Amione +Barzaghi +Brase +cpt +Crema +Damle +Francke +Ji +Kanefendt +Kaul +Leone +Ludden +Tennison +Unger +Xie diff --git a/Qualification/Input/Content/Carbamazepine-Alprazolam-DDI.md b/Qualification/Input/Content/Carbamazepine-Alprazolam-DDI.md new file mode 100644 index 0000000..7a77e08 --- /dev/null +++ b/Qualification/Input/Content/Carbamazepine-Alprazolam-DDI.md @@ -0,0 +1,8 @@ +The release of the snapshot containing the respective simulations can be found here: +https://github.com/Open-Systems-Pharmacology/Carbamazepine-Alprazolam-DDI/releases/tag/v1.0 + +The carbamazepine-alprazolam interaction was evaluated using one clinical DDI study ([Furukori 1998](#4-references)). + +| DataID | Enzyme | Perpetrator / victim | Study design | Clinical study | +| ------ | ------ | -------------------------- | ------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------ | +| 1457 | CYP3A4 | Carbamazepine / alprazolam | Carbamazepine: 100 mg po TID for 10 days
Alprazolam: 0.8 mg po single dose, 2 hours after the 22nd carbamazepine dose | [Furukori 1998](#4-references) | diff --git a/Qualification/Input/Content/Carbamazepine-Efavirenz-DDI.md b/Qualification/Input/Content/Carbamazepine-Efavirenz-DDI.md new file mode 100644 index 0000000..2f4030a --- /dev/null +++ b/Qualification/Input/Content/Carbamazepine-Efavirenz-DDI.md @@ -0,0 +1,8 @@ +The release of the snapshot containing the respective simulations can be found here: +https://github.com/Open-Systems-Pharmacology/Carbamazepine-Efavirenz-DDI/releases/tag/v1.0 + +The carbamazepine-efavirenz interaction was evaluated using one clinical DDI study ([Ji 2008](#4-references)). + +| DataID | Enzyme | Perpetrator / victim | Study design | Clinical study | +| ------ | ------ | ------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------ | +| 959 | CYP3A4 | Carbamazepine / efavirenz | Study Arm 1:
Carbamazepine (starting with the 15th dose of efavirenz): 200 mg po QD for 3 days, followed by 200 mg po BID for 3 days, followed by 400 mg po QD for 16 days
Efavirenz: 600 mg po QD for 35 days | [Ji 2008](#4-references) | diff --git a/Qualification/Input/Content/Carbamazepine-Midazolam-DDI.md b/Qualification/Input/Content/Carbamazepine-Midazolam-DDI.md new file mode 100644 index 0000000..240c1fb --- /dev/null +++ b/Qualification/Input/Content/Carbamazepine-Midazolam-DDI.md @@ -0,0 +1,10 @@ +The release of the snapshot containing the respective simulations can be found here: +https://github.com/Open-Systems-Pharmacology/Carbamazepine-Midazolam-DDI/releases/tag/v1.0 + +The carbamazepine-midazolam interaction was evaluated using three clinical DDI studies ([Lutz 2018](#4-references), [Kanefendt 2023](#4-references)). + +| DataID | Enzyme | Perpetrator / victim | Study design | Clinical study | +| ------ | ------ | ------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------- | +| 1460 | CYP3A4 | Carbamazepine / midazolam | Carbamazepine: 100 mg po BID for 2 days, followed by 200 mg po BID for 2 days, followed by 300 mg po BID for 22 days
Midazolam: 2 mg po single dose, concomitantly with the 49th carbamazepine dose | [Lutz 2018](#4-references) | +| 943 | CYP3A4 | Carbamazepine / midazolam | Carbamazepine: 100 mg po BID for 2 days, followed by 200 mg po BID for 2 days, followed by 300 mg po for 17 days
Midazolam: 1 mg po single dose, 10 hours after the 26th carbamazepine dose | [Kanefendt 2023](#4-references) | +| 1133 | CYP3A4 | Carbamazepine / midazolam | Carbamazepine: 100 mg po BID for 2 days, followed by 200 mg po BID for 2 days, followed by 300 mg po for 18 days
Midazolam: 1 mg po single dose, 12 hours after the 28th carbamazepine dose | [Kanefendt 2023](#4-references) | diff --git a/Qualification/Input/Content/Cimetidine-Carbamazepine-DDI.md b/Qualification/Input/Content/Cimetidine-Carbamazepine-DDI.md new file mode 100644 index 0000000..5166c67 --- /dev/null +++ b/Qualification/Input/Content/Cimetidine-Carbamazepine-DDI.md @@ -0,0 +1,8 @@ +The release of the snapshot containing the respective simulations can be found here: +https://github.com/Open-Systems-Pharmacology/Cimetidine-Carbamazepine-DDI/releases/tag/v1.1 + +The cimetidine-carbamazepine interaction was evaluated using one clinical DDI study ([Dalton 1985](#4-references)). + +| DataID | Enzyme | Perpetrator / victim | Study design | Comment | Clinical study | +| ------ | ------ | -------------------------- | ------------------------------------------------------------------------------------------------------------------------------------- | ------- | ---------------------------- | +| 900 | CYP3A4 | Cimetidine / carbamazepine | Cimetidine: 300 mg po QID for 9 days
Carbamazepine: 600 mg po single dose, one hour before the 9th dose of cimetidine | | [Dalton 1985](#4-references) | diff --git a/Qualification/Input/Content/Efavirenz-Carbamazepine-DDI.md b/Qualification/Input/Content/Efavirenz-Carbamazepine-DDI.md new file mode 100644 index 0000000..9dc2655 --- /dev/null +++ b/Qualification/Input/Content/Efavirenz-Carbamazepine-DDI.md @@ -0,0 +1,8 @@ +The release of the snapshot containing the respective simulations can be found here: +https://github.com/Open-Systems-Pharmacology/Efavirenz-Carbamazepine-DDI/releases/tag/v1.0 + +The efavirenz-carbamazepine interaction was evaluated using one clinical DDI study ([Ji 2008](#4-references)). + +| DataID | Enzyme | Perpetrator / victim | Study design | Clinical study | +| ------ | ------ | ------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------ | +| 961 | CYP3A4 | Efavirenz / carbamazepine | Study Arm 2:
Efavirenz (starting with the 25th dose of carbamazepine): 600 mg po QD for 14 days
Carbamazepine: 200 mg po QD for 3 days, followed by 200 mg po BID for 3 days, followed by 400 mg po QD for 30 days | [Ji 2008](#4-references) | diff --git a/Qualification/Input/Content/Erythromycin-Carbamazepine-DDI.md b/Qualification/Input/Content/Erythromycin-Carbamazepine-DDI.md new file mode 100644 index 0000000..8d18fcd --- /dev/null +++ b/Qualification/Input/Content/Erythromycin-Carbamazepine-DDI.md @@ -0,0 +1,11 @@ +The release of the snapshot containing the respective simulations can be found here: +https://github.com/Open-Systems-Pharmacology/Erythromycin-Carbamazepine-DDI/releases/tag/v1.1 + +The erythromycin-carbamazepine interaction was evaluated using three clinical DDI studies ([Barzaghi 1987](#4-references), [Miles 1989](#4-references), [Wong 1983](#4-references)). + +| DataID | Enzyme | Perpetrator / victim | Study design | Clinical study | +| ------ | ------ | ---------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------ | +| 465 | CYP3A4 | Erythromycin / carbamazepine | Erythromycin: 500 mg po TID for 10 days
Carbamazepine: 400 mg po single dose, administered on the 7th day of treatment with erythromycin | [Barzaghi 1987](#4-references) | +| 1157 | CYP3A4 | Erythromycin / carbamazepine | Erythromycin: 250 mg po QID for 3 days, starting on day 15 of carbamazepine administration
Carbamazepine: 300 mg po QD for 17 days | [Miles 1989](#4-references) | +| 1158 | CYP3A4 | Erythromycin / carbamazepine | Erythromycin: 250 mg po QID for 3 days, starting on day 15 of carbamazepine administration
Carbamazepine: 400 mg po QD for 17 days | [Miles 1989](#4-references) | +| 1154 | CYP3A4 | Erythromycin / carbamazepine | Erythromycin: 250 mg po QID for 8 days
Carbamazepine: 400 mg po single dose, administered on the 6th day of treatment with erythromycin | [Wong 1983](#4-references) | diff --git a/Qualification/Input/Content/Qualification_DDI_CYP3A4_network_description.md b/Qualification/Input/Content/Qualification_DDI_CYP3A4_network_description.md index 2a65818..3e1b9e4 100644 --- a/Qualification/Input/Content/Qualification_DDI_CYP3A4_network_description.md +++ b/Qualification/Input/Content/Qualification_DDI_CYP3A4_network_description.md @@ -1,29 +1,28 @@ - To qualify the OSP suite for the prediction of the CYP3A4 DDI potential of new drugs, a set of verified PBPK models of index perpetrators, covering the range from strong CYP3A4 induction to strong inhibition, and respective CYP3A4 DDI victim drugs is specified to set up a CYP3A4-mediated DDI modeling network. - The following perpetrator compounds were selected: - **Rifampicin** (strong CYP3A4 inducer) Model snapshot and evaluation plan (*release* **v1.2**): https://github.com/Open-Systems-Pharmacology/Rifampicin-Model/releases/tag/v1.2 +- **Carbamazepine** (moderate CYP3A4 inducer) + Model snapshot and evaluation plan (*release* **v1.3**): [https://github.com/Open-Systems-Pharmacology/Carbamazepine-Model/releases/tag/v1.3](https://github.com/Open-Systems-Pharmacology/Carbamazepine-Model/releases/tag/v1.3) - **Efavirenz** (moderate CYP3A4 inducer) Model snapshot and evaluation plan (*release* **v1.1**): https://github.com/Open-Systems-Pharmacology/Efavirenz-Model/releases/tag/v1.1 - **Cimetidine** (weak CYP3A4 inhibitor) - Model snapshot and evaluation plan (*release* **v1.1**): https://github.com/Open-Systems-Pharmacology/Cimetidine-Model/releases/tag/v1.1 + Model snapshot and evaluation plan (*release* **v1.2**): https://github.com/Open-Systems-Pharmacology/Cimetidine-Model/releases/tag/v1.2 - **Fluvoxamine** (weak/moderate CYP3A4 inhibitor) - Model snapshot and evaluation plan (*release* **v1.1**): https://github.com/Open-Systems-Pharmacology/Fluvoxamine-Model/releases/tag/v1.1 + Model snapshot and evaluation plan (*release* **v1.2**): https://github.com/Open-Systems-Pharmacology/Fluvoxamine-Model/releases/tag/v1.2 - **Verapamil** (moderate CYP3A4 inhibitor) Model snapshot and evaluation plan (*release* **v1.2**): https://github.com/Open-Systems-Pharmacology/Verapamil-Model/releases/tag/v1.2 - **Fluconazole** (moderate CYP3A4 inhibitor) Model snapshot and evaluation plan (*release* **v1.0**): https://github.com/Open-Systems-Pharmacology/Fluconazole-Model/releases/tag/v1.0 - **Erythromycin** (moderate CYP3A4 inhibitor) - Model snapshot and evaluation plan (*release* **v1.2**): https://github.com/Open-Systems-Pharmacology/Erythromycin-Model/releases/tag/v1.2 + Model snapshot and evaluation plan (*release* **v1.3**): https://github.com/Open-Systems-Pharmacology/Erythromycin-Model/releases/tag/v1.3 - **Clarithromycin** (strong CYP3A4 inhibitor) Model snapshot and evaluation plan (*release* **v1.2**): https://github.com/Open-Systems-Pharmacology/Clarithromycin-Model/releases/tag/v1.2 - **Itraconazole** including metabolites (strong CYP3A4 inhibitor) Model snapshot and evaluation plan (*release* **v1.3**): https://github.com/Open-Systems-Pharmacology/Itraconazole-Model/releases/tag/v1.3 - The following sensitive CYP3A4 substrates as victim drugs were selected: - **Midazolam** @@ -35,18 +34,11 @@ The following sensitive CYP3A4 substrates as victim drugs were selected: - **Alfentanil** Model snapshot and evaluation plan (*release* **v2.2**): https://github.com/Open-Systems-Pharmacology/Alfentanil-Model/releases/tag/v2.2 - - **Figure 1** shows the prespecified and developed DDI modeling network of interacting perpetrator and victim drugs for the OSP suite qualification of predicting CYP3A4-mediated DDI. - - **Figure** **1: CYP3A4 DDI modeling network** ![DDI CYP3A4 network](images/DDI_CYP3A4_Compound_Network.png) The arrows indicate where at least one clinical DDI study between the two connected substances was available and included in the model network. Red indicates inhibition and green indicates induction as the primary type of interaction. Thin arrows indicate weak, mid-thick arrows moderate and thick arrows strong CYP3A4 modulation by the perpetrator. - - The published DDI studies between the respective perpetrators and victim drugs were simulated and compared to observed data. The following sections give an overview of the clinical studies being part of this qualification report. The respective data identifier (DataID) refers to the **ID** of the dataset in the [OSP PK database](https://github.com/Open-Systems-Pharmacology/Database-for-observed-data). - diff --git a/Qualification/Input/Content/References.md b/Qualification/Input/Content/References.md index 60ae92f..29f5403 100644 --- a/Qualification/Input/Content/References.md +++ b/Qualification/Input/Content/References.md @@ -4,13 +4,23 @@ **OSP PK Database** (https://github.com/Open-Systems-Pharmacology/Database-for-observed-data) +## Carbamazepine-Alprazolam-DDI +**Furukori 1998** Furukori, H., Otani, K., Yasui, N., *et al.* (2018). Effect of carbamazepine on the single oral dose pharmacokinetics of alprazolam. *Neuropsychopharmacology*, *18*(5), 364-369. -## Cimetidine-Alfentanil-DDI +## Carbamazepine-Efavirenz-DDI -**Kienlen 1993** Kienlen, J., Levron, JC., Aubas, S. *et al.* Pharmacokinetics of Alfentanil in Patients Treated with Either Cimetidine or Ranitidine. Drug Invest **6,** 257–262 (1993). +**Ji 2008** Ji, P., Damle, B., Xie, J., Unger, S. E., Grasela, D. M., & Kaul, S. (2008). Pharmacokinetic interaction between efavirenz and carbamazepine after multiple‐dose administration in healthy subjects. *The Journal of Clinical Pharmacology*, *48*(8), 948-956. + +## Carbamazepine-Midazolam-DDI +**Lutz 2018** Lutz, J. D., Kirby, B. J., Wang, L., *et al.* (2018). Cytochrome P450 3A induction predicts P‐glycoprotein induction; part 2: prediction of decreased substrate exposure after rifabutin or carbamazepine. *Clinical Pharmacology & Therapeutics*, *104*(6), 1191-1198. +**Kanefendt 2023** Kanefendt, F., Dallmann, A., Chen, H., Francke, K., Liu, T., Brase, C., Frechen, S., & Schultze-Mosgau, M. H. (2024). Assessment of the CYP3A4 Induction Potential by Carbamazepine: Insights from two Clinical DDI Studies and PBPK Modeling. *Clinical pharmacology and therapeutics*. doi: 10.1002/cpt.3151. Epub ahead of print. + +## Cimetidine-Alfentanil-DDI + +**Kienlen 1993** Kienlen, J., Levron, JC., Aubas, S. *et al.* Pharmacokinetics of Alfentanil in Patients Treated with Either Cimetidine or Ranitidine. Drug Invest **6,** 257–262 (1993). ## Cimetidine-Alprazolam-DDI @@ -18,7 +28,9 @@ **Abernethy 1983** Abernethy DR, Greenblatt DJ, Divoll M, Moschitto LJ, Harmatz JS, Shader RI. Interaction of cimetidine with the triazolobenzodiazepines alprazolam and triazolam. Psychopharmacology (Berl). 1983;80(3):275-8. doi: 10.1007/BF00436169. +## Cimetidine-Carbamazepine-DDI +**Dalton 1985** Dalton, M. J., Powell, J. R., & Messenheimer Jr, J. A. (1985). The Influence of Cimetidine on Single‐Dose Carbamazepine Pharmacokinetics. *Epilepsia*, *26*(2), 127-130. ## Cimetidine-Midazolam-DDI @@ -32,8 +44,6 @@ **Salonen 1986** Salonen M, Aantaa E, Aaltonen L, Kanto J. Importance of the interaction of midazolam and cimetidine. Acta Pharmacol Toxicol (Copenh). 1986 Feb;58(2):91-5. - - ## Cimetidine-Triazolam-DDI **Pourbaix 1985** Pourbaix S, Desager JP, Hulhoven R, Smith RB, Harvengt C. Pharmacokinetic consequences of long term coadministration of cimetidine and triazolobenzodiazepines, alprazolam and triazolam, in healthy subjects. Int J Clin Pharmacol Ther Toxicol. 1985 Aug;23(8):447-51. @@ -44,14 +54,10 @@ **Friedman 1988** Friedman H, Greenblatt DJ, Burstein ES, Scavone JM, Harmatz JS, Shader RI. Triazolam kinetics: interaction with cimetidine, propranolol, and the combination. J Clin Pharmacol. 1988 Mar;28(3):228-33. - - ## Cimetidine-Verapamil-DDI **Smith 1984** Smith MS, Benyunes MC, Bjornsson TD, Shand DG, Pritchett EL. Influence of cimetidine on verapamil kinetics and dynamics. Clin Pharmacol Ther. 1984 Oct;36(4):551-4. - - ## Clarithromycin-Midazolam-DDI **Gorski 1998** Gorski, J. C., Jones, D. R., Haehner‐Daniels, B. D., Hamman, M. A., O'Mara Jr, E. M., & Hall, S. D. (1998). The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin. *Clinical Pharmacology & Therapeutics*, *64*(2), 133-143. @@ -70,13 +76,23 @@ **Yeates 1996** Yeates, R. A., Laufen, H., & Zimmermann, T. (1996). Interaction between midazolam and clarithromycin: comparison with azithromycin. *International journal of clinical pharmacology and therapeutics*, *34*(9), 400-405. - - ## Clarithromycin-Triazolam-DDI **Greenblatt 1998a** Greenblatt DJ, von Moltke LL, Harmatz JS, Counihan M, Graf JA, Durol AL, Mertzanis P, Duan SX, Wright CE, Shader RI. Inhibition of triazolam clearance by macrolide antimicrobial agents: in vitro correlates and dynamic consequences. Clin Pharmacol Ther. 1998 Sep;64(3):278-85. +## Efavirenz-Alfentanil-DDI + +**Kharasch 2012** Kharasch ED, Whittington D, Ensign D, Hoffer C, Bedynek PS, Campbell S, Stubbert K, Crafford A, London A, Kim T. Mechanism of efavirenz influence on methadone pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2012 Apr;91(4):673-84. + +## Efavirenz-Carbamazepine-DDI + +**Ji 2008** Ji, P., Damle, B., Xie, J., Unger, S. E., Grasela, D. M., & Kaul, S. (2008). Pharmacokinetic interaction between efavirenz and carbamazepine after multiple‐dose administration in healthy subjects. *The Journal of Clinical Pharmacology*, *48*(8), 948-956. + +## Efavirenz-Midazolam-DDI + +**Katzenmaier 2010** Katzenmaier S, Markert C, Mikus G. Proposal of a new limited sampling strategy to predict CYP3A activity using a partial AUC of midazolam. Eur J Clin Pharmacol. 2010 Nov;66(11):1137-41. +**Mikus 2017** Mikus G, Heinrich T, Bödigheimer J, Röder C, Matthee AK, Weiss J, Burhenne J, Haefeli WE. Semisimultaneous Midazolam Administration to Evaluate the Time Course of CYP3A Activation by a Single Oral Dose of Efavirenz. J Clin Pharmacol. 2017 Jul;57(7):899-905. ## Erythromycin-Alfentanil-DDI @@ -84,13 +100,17 @@ **Bartkowski 1993** Bartkowski, R. R., Goldberg, M. E., Huffnagle, S., & Epstein, R. H. (1993). Sufentanil disposition. Is it affected by erythromycin administration?. *Anesthesiology*, *78*(2), 260-265. - - ## Erythromycin-Alprazolam-DDI **Yasui 1996** Yasui, N., Otani, K., Kaneko, S., Ohkubo, T., Osanai, T., Sugawara, K., ... & Ishizaki, T. (1996). A kinetic and dynamic study of oral alprazolam with and without erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in alprazolam metabolism. *Clinical Pharmacology & Therapeutics*, *59*(5), 514-519. +## Erythromycin-Carbamazepine-DDI + +**Barzaghi 1987** Barzaghi, N., Gatti, G., Crema, F., Monteleone, M., Amione, C., Leone, L., & Perucca, E. (1987). Inhibition by erythromycin of the conversion of carbamazepine to its active 10, 11‐epoxide metabolite. *British journal of clinical pharmacology*, *24*(6), 836-838. +**Miles 1989** Miles, M. V., & Tennison, M. B. (1989). Erythromycin effects on multiple-dose carbamazepine kinetics. *Therapeutic drug monitoring*, *11*(1), 47-52. + +**Wong 1983** Wong, Y. Y., Ludden, T. M., & Bell, R. D. (1983). Effect of erythromycin on carbamazepine kinetics. *Clinical Pharmacology & Therapeutics*, *33*(4), 460-464. ## Erythromycin-Midazolam-DDI @@ -104,35 +124,29 @@ **Zimmermann 1996** Zimmermann, T., Yeates, R. A., Laufen, H., Scharpf, F., Leitold, M., & Wildfeuer, A. (1996). Influence of the antibiotics erythromycin and azithromycin on the pharmacokinetics and pharmacodynamics of midazolam. *Arzneimittel-Forschung*, *46*(2), 213-217. - - ## Erythromycin-Triazolam-DDI **Greenblatt 1998** Greenblatt, D. J., von Moltke, L. L., Harmatz, J. S., Counihan, M., Graf, J. A., Durol, A. L. B., ... & Shader, R. I. (1998). Inhibition of triazolam clearance by macrolide antimicrobial agents: in vitro correlates and dynamic consequences. *Clinical Pharmacology & Therapeutics*, *64*(3), 278-285. **Phillips 1986** Phillips, J. P., Antal, E. J., & Smith, R. B. (1986). A pharmacokinetic drug interaction between erythromycin and triazolam. *Journal of clinical psychopharmacology*, *6*(5), 297-299. - - ## Fluconazole-Alfentanil-DDI **Palkama 1998** Palkama, V. J., Isohanni, M. H., Neuvonen, P. J., & Olkkola, K. T. (1998). The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil. *Anesthesia & Analgesia*, *87*(1), 190-194. - - ## Fluconazole-Midazolam-DDI **Ahonen 1997** Ahonen, J., Olkkola, K. T., & Neuvonen, P. J. (1997). Effect of route of administration of fluconazole on the interaction between fluconazole and midazolam. *European journal of clinical pharmacology*, *51*(5), 415-419. **Olkkola 1996** Olkkola, K. T., Ahonen, J., & Neuvonen, P. J. (1996). The effect of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. *Anesthesia & Analgesia*, *82*(3), 511-516. - - ## Fluconazole-Triazolam-DDI **Varhe 1996** Varhe, A., Olkkola, K. T., & Neuvonen, P. J. (1996). Effect of fluconazole dose on the extent of fluconazole‐triazolam interaction. *British journal of clinical pharmacology*, *42*(4), 465-470. +## Fluvoxamine-Alprazolam-DDI +**Fleishaker 1994** Fleishaker, J. C., & Hulst, L. K. (1994). A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. *European journal of clinical pharmacology*, *46*(1), 35-39. ## Fluvoxamine-Midazolam-DDI @@ -140,20 +154,10 @@ **Lam 2003** Lam YW1, Alfaro CL, Ereshefsky L, Miller M. Pharmacokinetic and pharmacodynamic interactions of oral midazolam with ketoconazole, fluoxetine, fluvoxamine, and nefazodone. J Clin Pharmacol. 2003 Nov;43(11):1274-82. - - -## Fluvoxamine-Alprazolam-DDI - -**Fleishaker 1994** Fleishaker, J. C., & Hulst, L. K. (1994). A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. *European journal of clinical pharmacology*, *46*(1), 35-39. - - - ## Itraconazole-Alprazolam-DDI **Yasui 1998** Yasui N, Kondo T, Otani K, Furukori H, Kaneko S, Ohkubo T, Nagasaki T, Sugawara K. Effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam. Psychopharmacology (Berl). 1998 Oct;139(3):269-73. - - ## Itraconazole-Midazolam-DDI **Ahonen 1995** Ahonen J, Olkkola KT, Neuvonen PJ. Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers. Br J Clin Pharmacol. 1995 Sep;40(3):270-2. @@ -170,38 +174,12 @@ **Yu 2004** Yu KS, Cho JY, Jang IJ, Hong KS, Chung JY, Kim JR, Lim HS, Oh DS, Yi SY, Liu KH, Shin JG, Shin SG. Effect of the CYP3A5 genotype on the pharmacokinetics of intravenous midazolam during inhibited and induced metabolic states. Clin Pharmacol Ther. 2004 Aug;76(2):104-12. - - ## Itraconazole-Triazolam-DDI **Neuvonen 1996** Neuvonen PJ, Varhe A, Olkkola KT. The effect of ingestion time interval on the interaction between itraconazole and triazolam. Clin Pharmacol Ther. 1996 Sep;60(3):326-31. **Varhe 1994** Varhe A, Olkkola KT, Neuvonen PJ. Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther. 1994 Dec;56(6 Pt 1):601-7. - - -## Verapamil-Midazolam-DDI - -**Backman 1994** Backman JT, Olkkola KT, Aranko K, Himberg JJ, Neuvonen PJ. Dose of midazolam should be reduced during diltiazem and verapamil treatments. Br J Clin Pharmacol. 1994 Mar;37(3):221-5. - -**Wang 2005** Wang Y, Jin Y, Hilligoss JK, Ho H, Hamman MA, Hu Z, Gorski JD, Hall SD. Effect of CYP3A5 genotype on the extent of CYP3A inhibition by verapamil. Clin Pharmacol Ther. 2005; 77(2):P3. - - - -## Efavirenz-Alfentanil-DDI - -**Kharasch 2012** Kharasch ED, Whittington D, Ensign D, Hoffer C, Bedynek PS, Campbell S, Stubbert K, Crafford A, London A, Kim T. Mechanism of efavirenz influence on methadone pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2012 Apr;91(4):673-84. - - - -## Efavirenz-Midazolam-DDI - -**Katzenmaier 2010** Katzenmaier S, Markert C, Mikus G. Proposal of a new limited sampling strategy to predict CYP3A activity using a partial AUC of midazolam. Eur J Clin Pharmacol. 2010 Nov;66(11):1137-41. - -**Mikus 2017** Mikus G, Heinrich T, Bödigheimer J, Röder C, Matthee AK, Weiss J, Burhenne J, Haefeli WE. Semisimultaneous Midazolam Administration to Evaluate the Time Course of CYP3A Activation by a Single Oral Dose of Efavirenz. J Clin Pharmacol. 2017 Jul;57(7):899-905. - - - ## Rifampicin-Alfentanil-DDI **Kharasch 1997** Kharasch ED, Russell M, Mautz D, Thummel KE, Kunze KL, Bowdle A, Cox K. The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions. Anesthesiology. 1997 Jul;87(1):36-50. @@ -214,16 +192,12 @@ **Phimmasone 2001** Phimmasone S, Kharasch ED. A pilot evaluation of alfentanil-induced miosis as a noninvasive probe for hepatic cytochrome P450 3A4 (CYP3A4) activity in humans. Clin Pharmacol Ther. 2001 Dec;70(6):505-17. - - ## Rifampicin-Alprazolam-DDI **Gashaw 2003** Gashaw, I., Kirchheiner, J., Goldammer, M., Bauer, S., Seidemann, J., Zoller, K., ... & Brockmöller, J. (2003). Cytochrome p450 3A4 messenger ribonucleic acid induction by rifampin in human peripheral blood mononuclear cells: correlation with alprazolam pharmacokinetics. *Clinical Pharmacology & Therapeutics*, *74*(5), 448-457. **Schmider 1999** Schmider, J., Brockmöller, J., Arold, G., Bauer, S., & Roots, I. (1999). Simultaneous assessment of CYP3A4 and CYP1A2 activity in vivo with alprazolam and caffeine. *Pharmacogenetics*, *9*(6), 725-734. - - ## Rifampicin-Midazolam-DDI **Backman 1996** Backman JT, Olkkola KT, Neuvonen PJ. Rifampin drastically reduces plasma concentrations and effects of oral midazolam. Clin Pharmacol Ther. 1996 Jan;59(1):7-13. @@ -274,15 +248,16 @@ **Yu 2004** Yu KS, Cho JY, Jang IJ, Hong KS, Chung JY, Kim JR, Lim HS, Oh DS, Yi SY, Liu KH, Shin JG, Shin SG. Effect of the CYP3A5 genotype on the pharmacokinetics of intravenous midazolam during inhibited and induced metabolic states. Clin Pharmacol Ther. 2004 Aug;76(2):104-12. - - ## Rifampicin-Triazolam-DDI **Villikka 1997** Villikka K, Kivistö KT, Backman JT, Olkkola KT, & Neuvonen PJ. Triazolam is ineffective in patients taking rifampin. Clin Pharmacol Ther. 1997 Jan;61(1):8-14. - - ## Rifampicin-Verapamil-DDI **Barbarash 1988** Barbarash RA, Bauman JL, Fischer JH, Kondos GT, Batenhorst RL. Near-total reduction in verapamil bioavailability by rifampin. Electrocardiographic correlates. Chest. 1988 Nov;94(5):954-9. +## Verapamil-Midazolam-DDI + +**Backman 1994** Backman JT, Olkkola KT, Aranko K, Himberg JJ, Neuvonen PJ. Dose of midazolam should be reduced during diltiazem and verapamil treatments. Br J Clin Pharmacol. 1994 Mar;37(3):221-5. + +**Wang 2005** Wang Y, Jin Y, Hilligoss JK, Ho H, Hamman MA, Hu Z, Gorski JD, Hall SD. Effect of CYP3A5 genotype on the extent of CYP3A inhibition by verapamil. Clin Pharmacol Ther. 2005; 77(2):P3. diff --git a/Qualification/Input/Content/images/DDI_CYP3A4_Compound_Network.png b/Qualification/Input/Content/images/DDI_CYP3A4_Compound_Network.png index 47f8026..adf0880 100644 Binary files a/Qualification/Input/Content/images/DDI_CYP3A4_Compound_Network.png and b/Qualification/Input/Content/images/DDI_CYP3A4_Compound_Network.png differ diff --git a/Qualification/Input/Content/images/DDI_CYP3A4_Compound_Network.pptx b/Qualification/Input/Content/images/DDI_CYP3A4_Compound_Network.pptx index 0a4875f..f2c48d4 100644 Binary files a/Qualification/Input/Content/images/DDI_CYP3A4_Compound_Network.pptx and b/Qualification/Input/Content/images/DDI_CYP3A4_Compound_Network.pptx differ diff --git a/Qualification/Input/qualification_plan.json b/Qualification/Input/qualification_plan.json index dc8335e..a4abe0e 100644 --- a/Qualification/Input/qualification_plan.json +++ b/Qualification/Input/qualification_plan.json @@ -9,6 +9,10 @@ "Id": "Alprazolam", "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Alprazolam-Model/v1.1/Alprazolam-Model.json" }, + { + "Id": "Carbamazepine", + "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Carbamazepine-Model/v1.3/Carbamazepine-Model.json" + }, { "Id": "Cimetidine", "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Cimetidine-Model/v1.2/Cimetidine-Model.json" @@ -54,293 +58,867 @@ "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Verapamil-Model/v1.2/Verapamil-Model.json" }, { - "Id": "Cimetidine-Alfentanil-DDI", - "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Cimetidine-Alfentanil-DDI/v1.2/Cimetidine-Alfentanil-DDI.json", + "Id": "Carbamazepine-Alprazolam-DDI", + "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Carbamazepine-Alprazolam-DDI/v1.1/Carbamazepine-Alprazolam-DDI.json", "BuildingBlocks": [ { "Type": "Compound", - "Name": "Alfentanil", - "Project": "Alfentanil" + "Name": "Alprazolam", + "Project": "Alprazolam" + }, + { + "Type": "Formulation", + "Name": "Solanax", + "Project": "Alprazolam" }, { "Type": "Compound", - "Name": "Cimetidine", - "Project": "Cimetidine" + "Name": "Carbamazepine", + "Project": "Carbamazepine" + }, + { + "Type": "Formulation", + "Name": "CBZ_tabletIR_fasted (Tegretol)", + "Project": "Carbamazepine" } ], "SimulationParameters": [ { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Alfentanil|P (interstitial->intracellular)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Alfentanil|P (interstitial->intracellular)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Alfentanil|P (interstitial->intracellular)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Alfentanil|P (interstitial->intracellular)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Alfentanil|P (interstitial->intracellular)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|Caecum_int_Caecum_cell|Alfentanil|P (interstitial->intracellular)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|Caecum_int_Caecum_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Alfentanil|P (interstitial->intracellular)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Alfentanil|P (interstitial->intracellular)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Alfentanil|P (interstitial->intracellular)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Alfentanil|P (interstitial->intracellular)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|Rectum_int_Rectum_cell|Alfentanil|P (interstitial->intracellular)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|Rectum_int_Rectum_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Alfentanil|P (intracellular->interstitial)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Alprazolam|P (intracellular->interstitial)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Alfentanil|P (intracellular->interstitial)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Alprazolam|P (intracellular->interstitial)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Alfentanil|P (intracellular->interstitial)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Alprazolam|P (intracellular->interstitial)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Alfentanil|P (intracellular->interstitial)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Alprazolam|P (intracellular->interstitial)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Alfentanil|P (intracellular->interstitial)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Alprazolam|P (intracellular->interstitial)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|Caecum_int_Caecum_cell|Alfentanil|P (intracellular->interstitial)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|Caecum_int_Caecum_cell|Alprazolam|P (intracellular->interstitial)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Alfentanil|P (intracellular->interstitial)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Alprazolam|P (intracellular->interstitial)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Alfentanil|P (intracellular->interstitial)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Alprazolam|P (intracellular->interstitial)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Alfentanil|P (intracellular->interstitial)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Alprazolam|P (intracellular->interstitial)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Alfentanil|P (intracellular->interstitial)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Alprazolam|P (intracellular->interstitial)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] }, { - "Project": "Alfentanil", - "Simulation": "Kharasch 2011b, Alfentanil PO 4 mg", - "Path": "Neighborhoods|Rectum_int_Rectum_cell|Alfentanil|P (intracellular->interstitial)", + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|Rectum_int_Rectum_cell|Alprazolam|P (intracellular->interstitial)", "TargetSimulations": [ - "Kienlen 1993 - Alfentanil iv control", - "Kienlen 1993 - Alfentanil iv + Cimetidine iv" + "Furukori1998_ControlPhase", + "Furukori1998_TreatmentPhase" ] } ] }, { - "Id": "Cimetidine-Alprazolam-DDI", - "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Cimetidine-Alprazolam-DDI/v1.2/Cimetidine-Alprazolam-DDI.json", + "Id": "Carbamazepine-Efavirenz-DDI", + "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Carbamazepine-Efavirenz-DDI/v1.1/Carbamazepine-Efavirenz-DDI.json", "BuildingBlocks": [ { "Type": "Compound", - "Name": "Alprazolam", - "Project": "Alprazolam" + "Name": "Carbamazepine", + "Project": "Carbamazepine" }, { "Type": "Formulation", - "Name": "Xanax_IR", - "Project": "Alprazolam" + "Name": "CBZ_tabletIR_fasted (Tegretol)", + "Project": "Carbamazepine" }, { "Type": "Compound", - "Name": "Cimetidine", - "Project": "Cimetidine" + "Name": "Efavirenz", + "Project": "Efavirenz" }, { "Type": "Formulation", - "Name": "Tablet", - "Project": "Cimetidine" + "Name": "Sustiva", + "Project": "Efavirenz" } ], "SimulationParameters": [ + + ] + }, + { + "Id": "Carbamazepine-Midazolam-DDI", + "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Carbamazepine-Midazolam-DDI/v1.0/Carbamazepine-Midazolam-DDI.json", + "BuildingBlocks": [ { - "Project": "Alprazolam", - "Simulation": "PO_0.5mg", - "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Alprazolam|P (interstitial->intracellular)", - "TargetSimulations": [ - "Abernethy 1983 - Alprazolam 1 mg control", - "Abernethy 1983 - Alprazolam 1 mg + 300 mg cimetidine QID", - "Pourbaix 1985 - Alprazolam 0.5 mg TID control", - "Pourbaix 1985 - alprazolam 0.5 mg TID + cimetidine 200/400 mg QID" - ] + "Type": "Compound", + "Name": "Midazolam", + "Project": "Midazolam" }, { - "Project": "Alprazolam", - "Simulation": "PO_0.5mg", - "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Alprazolam|P (interstitial->intracellular)", - "TargetSimulations": [ - "Abernethy 1983 - Alprazolam 1 mg control", - "Abernethy 1983 - Alprazolam 1 mg + 300 mg cimetidine QID", - "Pourbaix 1985 - Alprazolam 0.5 mg TID control", - "Pourbaix 1985 - alprazolam 0.5 mg TID + cimetidine 200/400 mg QID" - ] + "Type": "Formulation", + "Name": "Oral solution", + "Project": "Midazolam" }, { - "Project": "Alprazolam", - "Simulation": "PO_0.5mg", - "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Alprazolam|P (interstitial->intracellular)", - "TargetSimulations": [ - "Abernethy 1983 - Alprazolam 1 mg control", - "Abernethy 1983 - Alprazolam 1 mg + 300 mg cimetidine QID", - "Pourbaix 1985 - Alprazolam 0.5 mg TID control", - "Pourbaix 1985 - alprazolam 0.5 mg TID + cimetidine 200/400 mg QID" - ] + "Type": "Compound", + "Name": "Carbamazepine", + "Project": "Carbamazepine" }, { - "Project": "Alprazolam", - "Simulation": "PO_0.5mg", - "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Alprazolam|P (interstitial->intracellular)", - "TargetSimulations": [ - "Abernethy 1983 - Alprazolam 1 mg control", - "Abernethy 1983 - Alprazolam 1 mg + 300 mg cimetidine QID", - "Pourbaix 1985 - Alprazolam 0.5 mg TID control", - "Pourbaix 1985 - alprazolam 0.5 mg TID + cimetidine 200/400 mg QID" - ] + "Type": "Formulation", + "Name": "CBZ_tabletIR_fasted (Tegretol)", + "Project": "Carbamazepine" }, { - "Project": "Alprazolam", + "Type": "Formulation", + "Name": "CBZ_capsuleXR_fasted (Carbatrol)", + "Project": "Carbamazepine" + } + ], + "SimulationParameters": [ + { + "Project": "Midazolam", + "Simulation": "po 3 mg (solution)", + "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", + "TargetSimulations": [ + "Kanefendt2023_Study1_ControlPhase", + "Kanefendt2023_Study1_TreatmentPhase", + "Kanefendt2023_Study2_ControlPhase", + "Kanefendt2023_Study2_TreatmentPhase", + "Lutz2018_ControlPhase", + "Lutz2018_TreatmentPhase" + ] + }, + { + "Project": "Midazolam", + "Simulation": "po 3 mg (solution)", + "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", + 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mg TID + cimetidine 200/400 mg QID" + ] + }, + { + "Project": "Alprazolam", + "Simulation": "PO_0.5mg", + "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Alprazolam|P (interstitial->intracellular)", + "TargetSimulations": [ + "Abernethy 1983 - Alprazolam 1 mg control", + "Abernethy 1983 - Alprazolam 1 mg + 300 mg cimetidine QID", + "Pourbaix 1985 - Alprazolam 0.5 mg TID control", + "Pourbaix 1985 - alprazolam 0.5 mg TID + cimetidine 200/400 mg QID" + ] + }, + { + "Project": "Alprazolam", "Simulation": "PO_0.5mg", "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Alprazolam|P (interstitial->intracellular)", "TargetSimulations": [ @@ -539,6 +1117,35 @@ } ] }, + { + "Id": "Cimetidine-Carbamazepine-DDI", + "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Cimetidine-Carbamazepine-DDI/v1.1/Cimetidine-Carbamazepine-DDI.json", + "BuildingBlocks": [ + { + "Type": "Compound", + "Name": "Cimetidine", + "Project": "Cimetidine" + }, + { + "Type": "Formulation", + "Name": "Tablet", + "Project": "Cimetidine" + }, + { + "Type": "Compound", + "Name": "Carbamazepine", + "Project": "Carbamazepine" + }, + { + "Type": "Formulation", + "Name": "CBZ_tabletIR_fasted (Tegretol)", + "Project": "Carbamazepine" + } + ], + "SimulationParameters": [ + + ] + }, { "Id": "Cimetidine-Midazolam-DDI", "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Cimetidine-Midazolam-DDI/v1.2/Cimetidine-Midazolam-DDI.json", @@ -2513,6 +3120,35 @@ } ] }, + { + "Id": "Efavirenz-Carbamazepine-DDI", + "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Efavirenz-Carbamazepine-DDI/v1.0/Efavirenz-Carbamazepine-DDI.json", + "BuildingBlocks": [ + { + "Type": "Compound", + "Name": "Carbamazepine", + "Project": "Carbamazepine" + }, + { + "Type": "Formulation", + "Name": "CBZ_tabletIR_fasted (Tegretol)", + "Project": "Carbamazepine" + }, + { + "Type": "Compound", + "Name": "Efavirenz", + "Project": "Efavirenz" + }, + { + "Type": "Formulation", + "Name": "Sustiva", + "Project": "Efavirenz" + } + ], + "SimulationParameters": [ + + ] + }, { "Id": "Erythromycin-Alfentanil-DDI", "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Erythromycin-Alfentanil-DDI/v1.2/Erythromycin-Alfentanil-DDI.json", @@ -2992,6 +3628,60 @@ } ] }, + { + "Id": "Erythromycin-Carbamazepine-DDI", + "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Erythromycin-Carbamazepine-DDI/v1.1/Erythromycin-Carbamazepine-DDI.json", + "BuildingBlocks": [ + { + "Type": "Individual", + "Name": "Barzaghi1987", + "Project": "Carbamazepine" + }, + { + "Type": "Individual", + "Name": "Miles1989", + "Project": "Carbamazepine" + }, + { + "Type": "Individual", + "Name": "Wong1983", + "Project": "Carbamazepine" + }, + { + "Type": "Compound", + "Name": "Carbamazepine", + "Project": "Carbamazepine" + }, + { + "Type": "Formulation", + "Name": "CBZ_tabletIR_fasted (Tegretol)", + "Project": "Carbamazepine" + }, + { + "Type": "Compound", + "Name": "Erythromycin", + "Project": "Erythromycin" + }, + { + "Type": "Formulation", + "Name": "Erythromycin_Weibull_enteric-coated-pellets", + "Project": "Erythromycin" + }, + { + "Type": "Formulation", + "Name": "Erythromycin_Weibull_filmtablet", + "Project": "Erythromycin" + }, + { + "Type": "Formulation", + "Name": "Erythromycin_Weibull_filmtablet_250mg", + "Project": "Erythromycin" + } + ], + "SimulationParameters": [ + + ] + }, { "Id": "Erythromycin-Midazolam-DDI", "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Erythromycin-Midazolam-DDI/v1.2/Erythromycin-Midazolam-DDI.json", @@ -10158,7 +10848,7 @@ "ObservedDataSets": [ { "Id": "DDI Ratios", - "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Database-for-observed-data/v1.4/DDI.csv", + "Path": "https://raw.githubusercontent.com/Open-Systems-Pharmacology/Database-for-observed-data/v1.5/DDI.csv", "Type": "DDIRatio" } ], @@ -10276,7 +10966,7 @@ "GOFMergedPlots": [], "ComparisonTimeProfilePlots": [ { - "SectionId": 301, + "SectionId": 304, "Title": "Kienlen 1993", "SimulationDuration": 10, "TimeUnit": "h", @@ -10306,7 +10996,7 @@ ] }, { - "SectionId": 302, + "SectionId": 305, "Title": "Abernethy 1983", "SimulationDuration": 24, "TimeUnit": "h", @@ -10336,7 +11026,7 @@ ] }, { - "SectionId": 302, + "SectionId": 305, "Title": "Pourbaix 1985", "SimulationDuration": 72, "TimeUnit": "h", @@ -10366,7 +11056,7 @@ ] }, { - "SectionId": 303, + "SectionId": 307, "Title": "Greenblatt 1986 (midazolam IV)", "SimulationDuration": 12, "TimeUnit": "h", @@ -10396,7 +11086,7 @@ ] }, { - "SectionId": 303, + "SectionId": 307, "Title": "Greenblatt 1986 (midazolam PO)", "SimulationDuration": 12, "TimeUnit": "h", @@ -10426,7 +11116,7 @@ ] }, { - "SectionId": 303, + "SectionId": 307, "Title": "Martinez 1999", "SimulationDuration": 24, "TimeUnit": "h", @@ -10456,7 +11146,7 @@ ] }, { - "SectionId": 303, + "SectionId": 307, "Title": "Fee 1987", "SimulationDuration": 15, "TimeUnit": "h", @@ -10486,7 +11176,7 @@ ] }, { - "SectionId": 303, + "SectionId": 307, "Title": "Salonen 1986", "SimulationDuration": 10, "TimeUnit": "h", @@ -10516,7 +11206,7 @@ ] }, { - "SectionId": 303, + "SectionId": 307, "Title": "Elliott 1984", "SimulationDuration": 15, "TimeUnit": "h", @@ -10546,7 +11236,7 @@ ] }, { - "SectionId": 304, + "SectionId": 308, "Title": "Abernethy 1983", "SimulationDuration": 20, "TimeUnit": "h", @@ -10576,7 +11266,7 @@ ] }, { - "SectionId": 304, + "SectionId": 308, "Title": "Friedman 1988", "SimulationDuration": 12, "TimeUnit": "h", @@ -10606,7 +11296,7 @@ ] }, { - "SectionId": 304, + "SectionId": 308, "Title": "Pourbaix 1985", "SimulationDuration": 24, "TimeUnit": "h", @@ -10636,7 +11326,7 @@ ] }, { - "SectionId": 304, + "SectionId": 308, "Title": "Cox 1986", "SimulationDuration": 15, "TimeUnit": "h", @@ -10666,7 +11356,7 @@ ] }, { - "SectionId": 305, + "SectionId": 309, "Title": "Smith 1984 (verapamil IV)", "SimulationDuration": 12, "TimeUnit": "h", @@ -10696,7 +11386,7 @@ ] }, { - "SectionId": 305, + "SectionId": 309, "Title": "Smith 1984 (verapamil PO)", "SimulationDuration": 12, "TimeUnit": "h", @@ -10726,7 +11416,7 @@ ] }, { - "SectionId": 306, + "SectionId": 310, "Title": "Gorski 1998 (midazolam IV)", "SimulationDuration": 14, "TimeUnit": "h", @@ -10756,7 +11446,7 @@ ] }, { - "SectionId": 306, + "SectionId": 310, "Title": "Gorski 1998 (midazolam po)", "SimulationDuration": 14, "TimeUnit": "h", @@ -10786,7 +11476,7 @@ ] }, { - "SectionId": 306, + "SectionId": 310, "Title": "Gurley 2006", "SimulationDuration": 10, "TimeUnit": "h", @@ -10816,7 +11506,7 @@ ] }, { - "SectionId": 306, + "SectionId": 310, "Title": "Gurley 2008a", "SimulationDuration": 10, "TimeUnit": "h", @@ -10846,7 +11536,7 @@ ] }, { - "SectionId": 306, + "SectionId": 310, "Title": "Markert 2013", "SimulationDuration": 20, "TimeUnit": "h", @@ -10876,7 +11566,7 @@ ] }, { - "SectionId": 306, + "SectionId": 310, "Title": "Prueksaritanont 2017", "SimulationDuration": 48, "TimeUnit": "h", @@ -10906,7 +11596,7 @@ ] }, { - "SectionId": 306, + "SectionId": 310, "Title": "Quinney 2008 (midazolam IV)", "SimulationDuration": 15, "TimeUnit": "h", @@ -10936,7 +11626,7 @@ ] }, { - "SectionId": 306, + "SectionId": 310, "Title": "Quinney 2008 (midazolam po)", "SimulationDuration": 15, "TimeUnit": "h", @@ -10966,7 +11656,7 @@ ] }, { - "SectionId": 306, + "SectionId": 310, "Title": "van Dyk 2018", "SimulationDuration": 10, "TimeUnit": "h", @@ -10996,7 +11686,7 @@ ] }, { - "SectionId": 306, + "SectionId": 310, "Title": "Yeates 1996", "SimulationDuration": 24, "TimeUnit": "h", @@ -11026,7 +11716,7 @@ ] }, { - "SectionId": 307, + "SectionId": 311, "Title": "Greenblatt 1998a", "SimulationDuration": 24, "TimeUnit": "h", @@ -11056,7 +11746,7 @@ ] }, { - "SectionId": 308, + "SectionId": 315, "Title": "Bartkowski 1989", "SimulationDuration": 10, "TimeUnit": "h", @@ -11097,7 +11787,7 @@ ] }, { - "SectionId": 308, + "SectionId": 315, "Title": "Bartkowski 1993", "SimulationDuration": 10, "TimeUnit": "h", @@ -11138,7 +11828,7 @@ ] }, { - "SectionId": 309, + "SectionId": 316, "Title": "Yasui 1996", "SimulationDuration": 48, "TimeUnit": "h", @@ -11168,7 +11858,7 @@ ] }, { - "SectionId": 310, + "SectionId": 318, "Title": "Carls 2014", "SimulationDuration": 12, "TimeUnit": "h", @@ -11209,7 +11899,7 @@ ] }, { - "SectionId": 310, + "SectionId": 318, "Title": "Okudaira 2007", "SimulationDuration": 24, "TimeUnit": "h", @@ -11261,7 +11951,7 @@ ] }, { - "SectionId": 310, + "SectionId": 318, "Title": "Olkkola 1993 (midazolam IV)", "SimulationDuration": 20, "TimeUnit": "h", @@ -11291,7 +11981,7 @@ ] }, { - "SectionId": 310, + "SectionId": 318, "Title": "Olkkola 1993 (midazolam po)", "SimulationDuration": 20, "TimeUnit": "h", @@ -11321,7 +12011,7 @@ ] }, { - "SectionId": 310, + "SectionId": 318, "Title": "Swart 2002", "SimulationDuration": 6, "TimeUnit": "h", @@ -11351,7 +12041,7 @@ ] }, { - "SectionId": 310, + "SectionId": 318, "Title": "Zimmermann 1996", "SimulationDuration": 24, "TimeUnit": "h", @@ -11381,7 +12071,7 @@ ] }, { - "SectionId": 311, + "SectionId": 319, "Title": "Greenblatt 1998", "SimulationDuration": 24, "TimeUnit": "h", @@ -11411,7 +12101,7 @@ ] }, { - "SectionId": 311, + "SectionId": 319, "Title": "Phillips 1986", "SimulationDuration": 24, "TimeUnit": "h", @@ -11441,7 +12131,7 @@ ] }, { - "SectionId": 312, + "SectionId": 323, "Title": "Fleishaker 1994 (Day 1, first dose)", "SimulationDuration": 6, "TimeUnit": "h", @@ -11471,7 +12161,7 @@ ] }, { - "SectionId": 312, + "SectionId": 323, "Title": "Fleishaker 1994 (Day 10)", "SimulationDuration": 24, "TimeUnit": "h", @@ -11501,7 +12191,7 @@ ] }, { - "SectionId": 313, + "SectionId": 324, "Title": "Kashuba 1998", "SimulationDuration": 24, "TimeUnit": "h", @@ -11531,7 +12221,7 @@ ] }, { - "SectionId": 313, + "SectionId": 324, "Title": "Lam 2003", "SimulationDuration": 24, "TimeUnit": "h", @@ -11561,7 +12251,7 @@ ] }, { - "SectionId": 314, + "SectionId": 325, "Title": "Yasui 1998", "SimulationDuration": 48, "TimeUnit": "h", @@ -11591,7 +12281,7 @@ ] }, { - "SectionId": 315, + "SectionId": 326, "Title": "Ahonen 1995", "SimulationDuration": 20, "TimeUnit": "h", @@ -11621,7 +12311,7 @@ ] }, { - "SectionId": 315, + "SectionId": 326, "Title": "Backman 1998", "SimulationDuration": 20, "TimeUnit": "h", @@ -11662,7 +12352,7 @@ ] }, { - "SectionId": 315, + "SectionId": 326, "Title": "Olkkola 1994", "SimulationDuration": 20, "TimeUnit": "h", @@ -11692,7 +12382,7 @@ ] }, { - "SectionId": 315, + "SectionId": 326, "Title": "Olkkola 1996 (day 1 po)", "SimulationDuration": 20, "TimeUnit": "h", @@ -11722,7 +12412,7 @@ ] }, { - "SectionId": 315, + "SectionId": 326, "Title": "Olkkola 1996 (day 4 iv)", "SimulationDuration": 20, "TimeUnit": "h", @@ -11752,7 +12442,7 @@ ] }, { - "SectionId": 315, + "SectionId": 326, "Title": "Olkkola 1996 (day 6 po)", "SimulationDuration": 20, "TimeUnit": "h", @@ -11782,7 +12472,7 @@ ] }, { - "SectionId": 315, + "SectionId": 326, "Title": "Prueksaritanont 2017", "SimulationDuration": 72, "TimeUnit": "h", @@ -11812,7 +12502,7 @@ ] }, { - "SectionId": 315, + "SectionId": 326, "Title": "Templeton 2010", "SimulationDuration": 24, "TimeUnit": "h", @@ -11864,7 +12554,7 @@ ] }, { - "SectionId": 315, + "SectionId": 326, "Title": "Yu 2004 (CYP3A5*3/*3)", "SimulationDuration": 24, "TimeUnit": "h", @@ -11894,7 +12584,7 @@ ] }, { - "SectionId": 316, + "SectionId": 327, "Title": "Neuvonen 1996", "SimulationDuration": 24, "TimeUnit": "h", @@ -11957,7 +12647,7 @@ ] }, { - "SectionId": 316, + "SectionId": 327, "Title": "Varhe 1994", "SimulationDuration": 24, "TimeUnit": "h", @@ -11987,7 +12677,7 @@ ] }, { - "SectionId": 317, + "SectionId": 333, "Title": "Backman 1994", "SimulationDuration": 20, "TimeUnit": "h", @@ -12017,7 +12707,7 @@ ] }, { - "SectionId": 317, + "SectionId": 333, "Title": "Wang 2005 (iv)", "SimulationDuration": 24, "TimeUnit": "h", @@ -12047,7 +12737,7 @@ ] }, { - "SectionId": 317, + "SectionId": 333, "Title": "Wang 2005 (po)", "SimulationDuration": 24, "TimeUnit": "h", @@ -12077,7 +12767,7 @@ ] }, { - "SectionId": 318, + "SectionId": 312, "Title": "Kharasch 2012 IV", "SimulationDuration": 7.5, "TimeUnit": "h", @@ -12107,7 +12797,7 @@ ] }, { - "SectionId": 318, + "SectionId": 312, "Title": "Kharasch 2012 PO", "SimulationDuration": 10, "TimeUnit": "h", @@ -12137,7 +12827,7 @@ ] }, { - "SectionId": 319, + "SectionId": 314, "Title": "Mikus 2017 IV", "SimulationDuration": 9, "TimeUnit": "h", @@ -12211,7 +12901,7 @@ ] }, { - "SectionId": 319, + "SectionId": 314, "Title": "Mikus 2017 PO", "SimulationDuration": 8, "TimeUnit": "h", @@ -12285,7 +12975,7 @@ ] }, { - "SectionId": 319, + "SectionId": 314, "Title": "Katzenmaier 2010", "SimulationDuration": 12, "TimeUnit": "h", @@ -12315,7 +13005,7 @@ ] }, { - "SectionId": 320, + "SectionId": 328, "Title": "Kharasch 1997", "SimulationDuration": 12, "TimeUnit": "h", @@ -12345,7 +13035,7 @@ ] }, { - "SectionId": 320, + "SectionId": 328, "Title": "Kharasch 2004 (iv)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12375,7 +13065,7 @@ ] }, { - "SectionId": 320, + "SectionId": 328, "Title": "Kharasch 2004 (po)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12405,7 +13095,7 @@ ] }, { - "SectionId": 320, + "SectionId": 328, "Title": "Kharasch 2011 (iv)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12468,7 +13158,7 @@ ] }, { - "SectionId": 320, + "SectionId": 328, "Title": "Kharasch 2011 (po)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12531,7 +13221,7 @@ ] }, { - "SectionId": 320, + "SectionId": 328, "Title": "Kharasch 2011b (iv during sequential administration of iv unlabeled alfentanil and oral deuterated alfentanil)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12561,7 +13251,7 @@ ] }, { - "SectionId": 320, + "SectionId": 328, "Title": "Kharasch 2011b (iv during simultaneous administration of iv unlabeled alfentanil and oral deuterated alfentanil)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12591,7 +13281,7 @@ ] }, { - "SectionId": 320, + "SectionId": 328, "Title": "Kharasch 2011b (po during sequential administration of iv unlabeled alfentanil and oral deuterated alfentanil)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12621,7 +13311,7 @@ ] }, { - "SectionId": 320, + "SectionId": 328, "Title": "Kharasch 2011b (po during simultaneous administration of iv unlabeled alfentanil and oral deuterated alfentanil)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12651,7 +13341,7 @@ ] }, { - "SectionId": 320, + "SectionId": 328, "Title": "Phimmasone 2001", "SimulationDuration": 24, "TimeUnit": "h", @@ -12681,7 +13371,7 @@ ] }, { - "SectionId": 321, + "SectionId": 329, "Title": "Gashaw 2003 (Day 7)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12711,7 +13401,7 @@ ] }, { - "SectionId": 321, + "SectionId": 329, "Title": "Gashaw 2003 (after washout phase)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12741,7 +13431,7 @@ ] }, { - "SectionId": 321, + "SectionId": 329, "Title": "Schmider 1999", "SimulationDuration": 24, "TimeUnit": "h", @@ -12771,7 +13461,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Backman 1996", "SimulationDuration": 24, "TimeUnit": "h", @@ -12801,7 +13491,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Backman 1998 (Phase IV and V vs. I)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12842,7 +13532,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Björkhem-Bergman 2013", "SimulationDuration": 10, "TimeUnit": "h", @@ -12894,7 +13584,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Chattopadhyay 2018", "SimulationDuration": 25, "TimeUnit": "h", @@ -12924,7 +13614,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Chung 2006", "SimulationDuration": 12, "TimeUnit": "h", @@ -12954,7 +13644,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Eap 2004 (7.5 mg)", "SimulationDuration": 12, "TimeUnit": "h", @@ -12984,7 +13674,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Gorski 2003 (iv)", "SimulationDuration": 12, "TimeUnit": "h", @@ -13014,7 +13704,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Gorski 2003 (po)", "SimulationDuration": 12, "TimeUnit": "h", @@ -13044,7 +13734,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Gurley 2006", "SimulationDuration": 12, "TimeUnit": "h", @@ -13074,7 +13764,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Gurley 2008a", "SimulationDuration": 12, "TimeUnit": "h", @@ -13104,7 +13794,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Kharasch 1997", "SimulationDuration": 15, "TimeUnit": "h", @@ -13134,7 +13824,7 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Kharasch 2004 (iv)", "SimulationDuration": 12, "TimeUnit": "h", @@ -13164,16 +13854,232 @@ ] }, { - "SectionId": 322, + "SectionId": 330, "Title": "Kharasch 2004 (po)", "SimulationDuration": 12, "TimeUnit": "h", "OutputMappings": [ { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Kharasch 2004 (po)", + "Simulation": "DDI Control - Midazolam - Kharasch 2004 (po)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2004 - po #1 Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)", + "StartTime": 0, + "TimeUnit": "h", + "Color": "#2166ac", + "Caption": "Control (without Rifampicin)", + "Symbol": "Circle" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2004", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2004 - po #1 with Perpetrator (Rifampicin) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)", + "StartTime": 128, + "TimeUnit": "h", + "Color": "#b2182b", + "Caption": "Treatment (with Rifampicin)", + "Symbol": "Square" + } + ] + }, + { + "SectionId": 330, + "Title": "Kharasch 2011 (iv)", + "SimulationDuration": 12, + "TimeUnit": "h", + "OutputMappings": [ + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Control - Midazolam - Kharasch 2011 (iv)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2011 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", + "StartTime": 0, + "TimeUnit": "h", + "Color": "#2166ac", + "Caption": "Control (without Rifampicin)", + "Symbol": "Circle" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 5 mg)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2011 - iv with Perpetrator (Rifampicin @ 5 mg) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", + "StartTime": 108, + "TimeUnit": "h", + "Color": "#e4948e", + "Caption": "Treatment (with 5 mg Rifampicin)", + "Symbol": "Square" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 10 mg)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2011 - iv with Perpetrator (Rifampicin @ 10 mg) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", + "StartTime": 108, + "TimeUnit": "h", + "Color": "#d6706b", + "Caption": "Treatment (with 10 mg Rifampicin)", + "Symbol": "Triangle" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 25 mg)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2011 - iv with Perpetrator (Rifampicin @ 25 mg) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", + "StartTime": 108, + "TimeUnit": "h", + "Color": "#c54a4a", + "Caption": "Treatment (with 25 mg Rifampicin)", + "Symbol": "Diamond" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 75 mg)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2011 - iv with Perpetrator (Rifampicin @ 75 mg) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", + "StartTime": 108, + "TimeUnit": "h", + "Color": "#b2182b", + "Caption": "Treatment (with 75 mg Rifampicin)", + "Symbol": "Asterisk" + } + ] + }, + { + "SectionId": 330, + "Title": "Kharasch 2011 (po)", + "SimulationDuration": 12, + "TimeUnit": "h", + "OutputMappings": [ + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Control - Midazolam - Kharasch 2011 (po)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2011 - po Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", + "StartTime": 0, + "TimeUnit": "h", + "Color": "#2166ac", + "Caption": "Control (without Rifampicin)", + "Symbol": "Circle" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 5 mg)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2011 - po with Perpetrator (Rifampicin @ 5 mg) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", + "StartTime": 132, + "TimeUnit": "h", + "Color": "#e4948e", + "Caption": "Treatment (with 5 mg Rifampicin)", + "Symbol": "Square" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 10 mg)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2011 - po with Perpetrator (Rifampicin @ 10 mg) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", + "StartTime": 132, + "TimeUnit": "h", + "Color": "#d6706b", + "Caption": "Treatment (with 10 mg Rifampicin)", + "Symbol": "Triangle" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 25 mg)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2011 - po with Perpetrator (Rifampicin @ 25 mg) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", + "StartTime": 132, + "TimeUnit": "h", + "Color": "#c54a4a", + "Caption": "Treatment (with 25 mg Rifampicin)", + "Symbol": "Diamond" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 75 mg)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kharasch 2011 - po with Perpetrator (Rifampicin @ 75 mg) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", + "StartTime": 132, + "TimeUnit": "h", + "Color": "#b2182b", + "Caption": "Treatment (with 75 mg Rifampicin)", + "Symbol": "Asterisk" + } + ] + }, + { + "SectionId": 330, + "Title": "Kim 2018", + "SimulationDuration": 12, + "TimeUnit": "h", + "OutputMappings": [ + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Control - Midazolam - Kim 2018 (male)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": [], + "StartTime": 0, + "TimeUnit": "h", + "Color": "#2166ac", + "Caption": "Control (without Rifampicin)", + "Symbol": "Circle" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kim 2018 (male)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": [], + "StartTime": 216, + "TimeUnit": "h", + "Color": "#b2182b", + "Caption": "Treatment (with Rifampicin)", + "Symbol": "Square" + } + ] + }, + { + "SectionId": 330, + "Title": "Link 2008 (iv)", + "SimulationDuration": 24, + "TimeUnit": "h", + "OutputMappings": [ + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Control - Midazolam - Link 2008 (iv)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Link 2008 - iv Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)", + "StartTime": 0, + "TimeUnit": "h", + "Color": "#2166ac", + "Caption": "Control (without Rifampicin)", + "Symbol": "Circle" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Link 2008 (iv)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Link 2008 - iv with Perpetrator (Rifampicin) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)", + "StartTime": 144, + "TimeUnit": "h", + "Color": "#b2182b", + "Caption": "Treatment (with Rifampicin)", + "Symbol": "Square" + } + ] + }, + { + "SectionId": 330, + "Title": "Link 2008 (po)", + "SimulationDuration": 24, + "TimeUnit": "h", + "OutputMappings": [ + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Control - Midazolam - Link 2008 (po)", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2004 - po #1 Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)", + "ObservedData": "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", @@ -13182,10 +14088,10 @@ }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2004", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Link 2008 (po)", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2004 - po #1 with Perpetrator (Rifampicin) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)", - "StartTime": 128, + "ObservedData": "Link 2008 - po with Perpetrator (Rifampicin) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)", + "StartTime": 144, "TimeUnit": "h", "Color": "#b2182b", "Caption": "Treatment (with Rifampicin)", @@ -13194,79 +14100,90 @@ ] }, { - "SectionId": 322, - "Title": "Kharasch 2011 (iv)", - "SimulationDuration": 12, + "SectionId": 330, + "Title": "Lutz 2008", + "SimulationDuration": 14, "TimeUnit": "h", "OutputMappings": [ { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Kharasch 2011 (iv)", + "Simulation": "DDI Control - Midazolam - Lutz 2018 (po)", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2011 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", + "ObservedData": "Lutz 2018 - Cohort 1, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without Rifampicin)", + "Caption": "Control Cohort 1 (without Rifampicin)", "Symbol": "Circle" }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 5 mg)", + "Simulation": "DDI Control - Midazolam - Lutz 2018 (po)", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2011 - iv with Perpetrator (Rifampicin @ 5 mg) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", - "StartTime": 108, + "ObservedData": "Lutz 2018 - Cohort 2, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", + "StartTime": 0, "TimeUnit": "h", - "Color": "#e4948e", - "Caption": "Treatment (with 5 mg Rifampicin)", + "Color": "#2166ac", + "Caption": "Control Cohort 2 (without Rifampicin)", "Symbol": "Square" }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 10 mg)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Lutz 2018 (Cohort 2, 2 and 600 mg RIF)", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2011 - iv with Perpetrator (Rifampicin @ 10 mg) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", - "StartTime": 108, + "ObservedData": "Lutz 2018 - Cohort 2, 2 mg Rifampicin - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", + "StartTime": 228, + "TimeUnit": "h", + "Color": "#e4948e", + "Caption": "Treatment Cohort 2 (2 mg Rifampicin)", + "Symbol": "Cross" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Lutz 2018 (Cohort 1, 10 and 75 mg RIF)", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Lutz 2018 - Cohort 1, 10 mg Rifampicin - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", + "StartTime": 228, "TimeUnit": "h", "Color": "#d6706b", - "Caption": "Treatment (with 10 mg Rifampicin)", - "Symbol": "Triangle" + "Caption": "Treatment Cohort 1 (10 mg Rifampicin)", + "Symbol": "Asterisk" }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 25 mg)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Lutz 2018 (Cohort 1, 10 and 75 mg RIF)", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2011 - iv with Perpetrator (Rifampicin @ 25 mg) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", - "StartTime": 108, + "ObservedData": "Lutz 2018 - Cohort 1, 75 mg Rifampicin - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", + "StartTime": 660, "TimeUnit": "h", "Color": "#c54a4a", - "Caption": "Treatment (with 25 mg Rifampicin)", + "Caption": "Treatment Cohort 1 (10 mg Rifampicin)", "Symbol": "Diamond" }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 75 mg)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Lutz 2018 (Cohort 2, 2 and 600 mg RIF)", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2011 - iv with Perpetrator (Rifampicin @ 75 mg) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", - "StartTime": 108, + "ObservedData": "Lutz 2018 - Cohort 2, 600 mg Rifampicin - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", + "StartTime": 660, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with 75 mg Rifampicin)", - "Symbol": "Asterisk" + "Caption": "Treatment Cohort 2 (2 mg Rifampicin)", + "Symbol": "Triangle" } ] }, { - "SectionId": 322, - "Title": "Kharasch 2011 (po)", + "SectionId": 330, + "Title": "Phimmasone 2001", "SimulationDuration": 12, "TimeUnit": "h", "OutputMappings": [ { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Kharasch 2011 (po)", + "Simulation": "DDI Control - Midazolam - Phimmasone 2001", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2011 - po Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", + "ObservedData": "Phimmasone 2001 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", @@ -13275,61 +14192,110 @@ }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 5 mg)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Phimmasone 2001", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2011 - po with Perpetrator (Rifampicin @ 5 mg) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", - "StartTime": 132, + "ObservedData": "Phimmasone 2001 - with Perpetrator (Rifampicin) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)", + "StartTime": 106, "TimeUnit": "h", - "Color": "#e4948e", - "Caption": "Treatment (with 5 mg Rifampicin)", + "Color": "#b2182b", + "Caption": "Treatment (with Rifampicin)", "Symbol": "Square" + } + ] + }, + { + "SectionId": 330, + "Title": "Prueksaritanont 2017", + "SimulationDuration": 24, + "TimeUnit": "h", + "OutputMappings": [ + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Control - Midazolam - Prueksaritanont 2017", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Prueksaritanont 2017 - Midazolam in microdosecocktail alone - Midazolam - PO - 10 µg - Plasma - agg. (n=12)", + "StartTime": 0, + "TimeUnit": "h", + "Color": "#2166ac", + "Caption": "Control (without Rifampicin)", + "Symbol": "Circle" }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 10 mg)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Prueksaritanont 2017", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2011 - po with Perpetrator (Rifampicin @ 10 mg) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", - "StartTime": 132, + "ObservedData": "Prueksaritanont 2017 - Midazolam in microdosecocktail + Rifampin - Midazolam - PO - 10 µg - Plasma - agg. (n=8)", + "StartTime": 0, "TimeUnit": "h", - "Color": "#d6706b", - "Caption": "Treatment (with 10 mg Rifampicin)", - "Symbol": "Triangle" + "Color": "#b2182b", + "Caption": "Treatment (with Rifampicin)", + "Symbol": "Square" + } + ] + }, + { + "SectionId": 330, + "Title": "Reitman 2011", + "SimulationDuration": 15, + "TimeUnit": "h", + "OutputMappings": [ + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Reitman 2011", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Reitman 2011 - Week 0 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)", + "StartTime": 648, + "TimeUnit": "h", + "Color": "#b2182b", + "Caption": "Week 0 after treatment with rifampicin", + "Symbol": "Square" }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 25 mg)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Reitman 2011", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2011 - po with Perpetrator (Rifampicin @ 25 mg) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", - "StartTime": 132, + "ObservedData": "Reitman 2011 - Week 1 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)", + "StartTime": 816, "TimeUnit": "h", "Color": "#c54a4a", - "Caption": "Treatment (with 25 mg Rifampicin)", + "Caption": "Week 1 after treatment with rifampicin", + "Symbol": "Triangle" + }, + { + "Project": "Rifampicin-Midazolam-DDI", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Reitman 2011", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Reitman 2011 - Week 2 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)", + "StartTime": 984, + "TimeUnit": "h", + "Color": "#d6706b", + "Caption": "Week 2 after treatment with rifampicin", "Symbol": "Diamond" }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kharasch 2011 (RIF @ 75 mg)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Reitman 2011", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Kharasch 2011 - po with Perpetrator (Rifampicin @ 75 mg) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", - "StartTime": 132, + "ObservedData": "Reitman 2011 - Week 4 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)", + "StartTime": 1320, "TimeUnit": "h", - "Color": "#b2182b", - "Caption": "Treatment (with 75 mg Rifampicin)", - "Symbol": "Asterisk" + "Color": "#e4948e", + "Caption": "Week 4 after treatment with rifampicin", + "Symbol": "Circle" } ] }, { - "SectionId": 322, - "Title": "Kim 2018", - "SimulationDuration": 12, + "SectionId": 330, + "Title": "Shin 2013", + "SimulationDuration": 24, "TimeUnit": "h", "OutputMappings": [ { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Kim 2018 (male)", + "Simulation": "DDI Control - Midazolam - Shin 2013", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": [], + "ObservedData": "Shin 2013 - Control phase (Midazolam alone) - Midazolam - IV - 1 mg - Plasma - agg. (n=24)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", @@ -13338,9 +14304,9 @@ }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Kim 2018 (male)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Shin 2013", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": [], + "ObservedData": "Shin 2013 - CYP3A4 induced phase (Midazolam + rifampicin) - Midazolam - IV - 2.5 mg - Plasma - agg. (n=24)", "StartTime": 216, "TimeUnit": "h", "Color": "#b2182b", @@ -13350,16 +14316,16 @@ ] }, { - "SectionId": 322, - "Title": "Link 2008 (iv)", + "SectionId": 330, + "Title": "Shin 2016", "SimulationDuration": 24, "TimeUnit": "h", "OutputMappings": [ { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Link 2008 (iv)", + "Simulation": "DDI Control - Midazolam - Shin 2016", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Link 2008 - iv Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)", + "ObservedData": "Shin 2016 - Midazolam alone - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", @@ -13368,10 +14334,10 @@ }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Link 2008 (iv)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Shin 2016", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Link 2008 - iv with Perpetrator (Rifampicin) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)", - "StartTime": 144, + "ObservedData": "Shin 2016 - Midazolam + rifampicin - Midazolam - IV - 2.5 mg - Plasma - agg. (n=12)", + "StartTime": 216, "TimeUnit": "h", "Color": "#b2182b", "Caption": "Treatment (with Rifampicin)", @@ -13380,16 +14346,16 @@ ] }, { - "SectionId": 322, - "Title": "Link 2008 (po)", - "SimulationDuration": 24, + "SectionId": 330, + "Title": "Szalat 2007", + "SimulationDuration": 6, "TimeUnit": "h", "OutputMappings": [ { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Link 2008 (po)", + "Simulation": "DDI Control - Midazolam - Szalat 2007", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)", + "ObservedData": "Szalat 2007 - Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", @@ -13398,10 +14364,10 @@ }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Link 2008 (po)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Szalat 2007", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Link 2008 - po with Perpetrator (Rifampicin) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)", - "StartTime": 144, + "ObservedData": "Szalat 2007 - with Perpetrator (Rifampicin) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)", + "StartTime": 132, "TimeUnit": "h", "Color": "#b2182b", "Caption": "Treatment (with Rifampicin)", @@ -13410,90 +14376,87 @@ ] }, { - "SectionId": 322, - "Title": "Lutz 2008", - "SimulationDuration": 14, + "SectionId": 330, + "Title": "van Dyk 2018", + "SimulationDuration": 12, "TimeUnit": "h", "OutputMappings": [ { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Lutz 2018 (po)", + "Simulation": "DDI Control - Midazolam - van Dyk 2018", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Lutz 2018 - Cohort 1, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", + "ObservedData": "van Dyk 2018 - Midazolam in Caucasian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=19)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control Cohort 1 (without Rifampicin)", + "Caption": "Control (without Rifampicin)", "Symbol": "Circle" }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Lutz 2018 (po)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - van Dyk 2018", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Lutz 2018 - Cohort 2, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", - "StartTime": 0, + "ObservedData": [], + "StartTime": 156, "TimeUnit": "h", - "Color": "#2166ac", - "Caption": "Control Cohort 2 (without Rifampicin)", + "Color": "#b2182b", + "Caption": "Treatment (with Rifampicin)", "Symbol": "Square" - }, - { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Lutz 2018 (Cohort 2, 2 and 600 mg RIF)", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Lutz 2018 - Cohort 2, 2 mg Rifampicin - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", - "StartTime": 228, - "TimeUnit": "h", - "Color": "#e4948e", - "Caption": "Treatment Cohort 2 (2 mg Rifampicin)", - "Symbol": "Cross" - }, + } + ] + }, + { + "SectionId": 330, + "Title": "Wiesinger 2020", + "SimulationDuration": 24, + "TimeUnit": "h", + "OutputMappings": [ { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Lutz 2018 (Cohort 1, 10 and 75 mg RIF)", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Lutz 2018 - Cohort 1, 10 mg Rifampicin - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", - "StartTime": 228, + "Simulation": "DDI Control - Midazolam - Wiesinger 2020", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Wiesinger 2020 - Control phase (no RIF) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)", + "StartTime": 0, "TimeUnit": "h", - "Color": "#d6706b", - "Caption": "Treatment Cohort 1 (10 mg Rifampicin)", - "Symbol": "Asterisk" + "Color": "#2166ac", + "Caption": "Control (without Rifampicin)", + "Symbol": "Circle" }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Lutz 2018 (Cohort 1, 10 and 75 mg RIF)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Wiesinger 2020", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Lutz 2018 - Cohort 1, 75 mg Rifampicin - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", - "StartTime": 660, + "ObservedData": "Wiesinger 2020 - Weak-induction phase (RIF 10 mg) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)", + "StartTime": 180, "TimeUnit": "h", "Color": "#c54a4a", - "Caption": "Treatment Cohort 1 (10 mg Rifampicin)", - "Symbol": "Diamond" + "Caption": "Treatment (low dose 10 mg Rifampicin)", + "Symbol": "Triangle" }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Lutz 2018 (Cohort 2, 2 and 600 mg RIF)", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Wiesinger 2020", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Lutz 2018 - Cohort 2, 600 mg Rifampicin - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", - "StartTime": 660, + "ObservedData": "Wiesinger 2020 - Strong-induction phase (RIF 600 mg) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)", + "StartTime": 444, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment Cohort 2 (2 mg Rifampicin)", - "Symbol": "Triangle" + "Caption": "Treatment (high dose 600 mg Rifampicin)", + "Symbol": "Square" } ] }, { - "SectionId": 322, - "Title": "Phimmasone 2001", - "SimulationDuration": 12, + "SectionId": 330, + "Title": "Yu 2004 (CYP3A5*3/*3)", + "SimulationDuration": 15, "TimeUnit": "h", "OutputMappings": [ { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Phimmasone 2001", + "Simulation": "DDI Control - Midazolam - Yu 2018 (CYP3A5 s3,s3)", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Phimmasone 2001 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)", + "ObservedData": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", @@ -13502,10 +14465,10 @@ }, { "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Phimmasone 2001", + "Simulation": "DDI Treatment - Rifampicin/Midazolam - Yu 2004 (CYP3A5 s3,s3)", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Phimmasone 2001 - with Perpetrator (Rifampicin) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)", - "StartTime": 106, + "ObservedData": "Yu 2004 - Treatment Rifampicin CYP3A5*3/*3 - Midazolam - IV - 2 mg - Plasma - agg. (n=7)", + "StartTime": 240, "TimeUnit": "h", "Color": "#b2182b", "Caption": "Treatment (with Rifampicin)", @@ -13514,16 +14477,16 @@ ] }, { - "SectionId": 322, - "Title": "Prueksaritanont 2017", - "SimulationDuration": 24, + "SectionId": 331, + "Title": "Villikka 1997", + "SimulationDuration": 12, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Prueksaritanont 2017", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Prueksaritanont 2017 - Midazolam in microdosecocktail alone - Midazolam - PO - 10 µg - Plasma - agg. (n=12)", + "Project": "Rifampicin-Triazolam-DDI", + "Simulation": "Villikka 1997 - Triazolam control - 0.5 mg SD PO", + "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Villikka 1997 - Triazolam + placebo - Triazolam - PO - 0.5 mg - Plasma - agg. (n=10)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", @@ -13531,572 +14494,659 @@ "Symbol": "Circle" }, { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Prueksaritanont 2017", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Prueksaritanont 2017 - Midazolam in microdosecocktail + Rifampin - Midazolam - PO - 10 µg - Plasma - agg. (n=8)", + "Project": "Rifampicin-Triazolam-DDI", + "Simulation": "Villikka 1997 - Rifampicin 600 mg over 5 days and Triazolam 0.5 mg SD PO", + "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Villikka 1997 - Treatment arm (pretreatment with rifampin; 600 mg; 5 days) - Triazolam - PO - 0.5 mg - Plasma - agg. (n=10)", + "StartTime": 113, + "TimeUnit": "h", + "Color": "#b2182b", + "Caption": "Treatment with Rifampicin", + "Symbol": "Square" + } + ] + }, + { + "SectionId": 332, + "Title": "Barbarash 1988 (verapamil IV)", + "SimulationDuration": 15, + "TimeUnit": "h", + "OutputMappings": [ + { + "Project": "Rifampicin-Verapamil-DDI", + "Simulation": "DDI Control - Verapamil - Barbarash 1988 (iv)", + "Output": "Organism|PeripheralVenousBlood|Verapamil|Plasma (Peripheral Venous Blood)", + "ObservedData": "Barbarash 1988 - Verapamil IV control - Verapamil - IV - 10 mg - Serum - agg. (n=6)", "StartTime": 0, "TimeUnit": "h", + "Color": "#2166ac", + "Caption": "Control (without Rifampicin)", + "Symbol": "Circle" + }, + { + "Project": "Rifampicin-Verapamil-DDI", + "Simulation": "DDI Treatment - Rifampicin/Verapamil - Barbarash 1988 (iv)", + "Output": "Organism|PeripheralVenousBlood|Verapamil|Plasma (Peripheral Venous Blood)", + "ObservedData": "Barbarash 1988 - Verapamil IV after 2 weeks of Rifampicin therapy - Verapamil - IV - 10 mg - Serum - agg. (n=6)", + "StartTime": 300, + "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with Rifampicin)", + "Caption": "Treatment with Rifampicin", "Symbol": "Square" } ] }, { - "SectionId": 322, - "Title": "Reitman 2011", + "SectionId": 332, + "Title": "Barbarash 1988 (verapamil PO)", "SimulationDuration": 15, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Reitman 2011", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Reitman 2011 - Week 0 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)", - "StartTime": 648, + "Project": "Rifampicin-Verapamil-DDI", + "Simulation": "DDI Control - Verapamil - Barbarash 1988 (po)", + "Output": "Organism|PeripheralVenousBlood|Verapamil|Plasma (Peripheral Venous Blood)", + "ObservedData": "Barbarash 1988 - Verapamil PO control - Verapamil - PO - 120 mg - Serum - agg. (n=6)", + "StartTime": 0, + "TimeUnit": "h", + "Color": "#2166ac", + "Caption": "Control (without Rifampicin)", + "Symbol": "Circle" + }, + { + "Project": "Rifampicin-Verapamil-DDI", + "Simulation": "DDI Treatment - Rifampicin/Verapamil - Barbarash 1988 (po)", + "Output": "Organism|PeripheralVenousBlood|Verapamil|Plasma (Peripheral Venous Blood)", + "ObservedData": "Barbarash 1988 - Verapamil PO after 2 weeks of Rifampicin therapy - Verapamil - PO - 120 mg - Serum - agg. (n=6)", + "StartTime": 348, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Week 0 after treatment with rifampicin", + "Caption": "Treatment with Rifampicin", + "Symbol": "Square" + } + ] + }, + { + "SectionId": 320, + "Title": "Palkama 1998", + "SimulationDuration": 10, + "TimeUnit": "h", + "OutputMappings": [ + { + "Project": "Fluconazole-Alfentanil-DDI", + "Simulation": "Alfentanil placebo", + "Output": "Organism|PeripheralVenousBlood|Alfentanil|Plasma (Peripheral Venous Blood)", + "ObservedData": "Palkama 1998 - Alfentanil placebo - Alfentanil - IV - 20 µg/kg - Plasma - agg. (n=9)", + "StartTime": 1, + "TimeUnit": "h", + "Color": "#2166ac", + "Caption": "Control (without fluconazole)", + "Symbol": "Circle" + }, + { + "Project": "Fluconazole-Alfentanil-DDI", + "Simulation": "Alfentanil -Fluconzole i.v. DDI", + "Output": "Organism|PeripheralVenousBlood|Alfentanil|Plasma (Peripheral Venous Blood)", + "ObservedData": "Palkama 1998 - Alfentanil with perpetrator fluconazole i.v. - Alfentanil - IV - 20 µg/kg - Plasma - agg. (n=9)", + "StartTime": 1, + "TimeUnit": "h", + "Color": "#b2182b", + "Caption": "Treatment (with intravenous fluconazole)", "Symbol": "Square" }, { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Reitman 2011", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Reitman 2011 - Week 1 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)", - "StartTime": 816, + "Project": "Fluconazole-Alfentanil-DDI", + "Simulation": "Alfentanil -Fluconzole oral. DDI", + "Output": "Organism|PeripheralVenousBlood|Alfentanil|Plasma (Peripheral Venous Blood)", + "ObservedData": "Palkama 1998 - Alfentanil with perpetrator fluconazole po - Alfentanil - IV - 20 µg/kg - Plasma - agg. (n=9)", + "StartTime": 1, "TimeUnit": "h", "Color": "#c54a4a", - "Caption": "Week 1 after treatment with rifampicin", + "Caption": "Treatment (with oral fluconazole)", "Symbol": "Triangle" + } + ] + }, + { + "SectionId": 321, + "Title": "Ahonen 1997", + "SimulationDuration": 17, + "TimeUnit": "h", + "OutputMappings": [ + { + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Ahonen_midazolam_po_7.5mg_placebo", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Ahonen 1997 - Midazolam placebo - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)", + "StartTime": 1, + "TimeUnit": "h", + "Color": "#2166ac", + "Caption": "Control (without fluconazole)", + "Symbol": "Circle" }, { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Reitman 2011", + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Ahonen_midazolam_po_7.5mg_fluconazole_400mg_i.v_DDI", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Reitman 2011 - Week 2 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)", - "StartTime": 984, + "ObservedData": "Ahonen 1997 - Midazolam with perpetrator fluconazole i.v - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)", + "StartTime": 1, "TimeUnit": "h", - "Color": "#d6706b", - "Caption": "Week 2 after treatment with rifampicin", - "Symbol": "Diamond" + "Color": "#b2182b", + "Caption": "Treatment (with intravenous fluconazole)", + "Symbol": "Square" }, { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Reitman 2011", + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Ahonen_midazolam_po_7.5mg_fluconazole_400mg_po_DDI", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Reitman 2011 - Week 4 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)", - "StartTime": 1320, + "ObservedData": "Ahonen 1997 - Midazolam with perpetrator fluconazole oral - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)", + "StartTime": 1, "TimeUnit": "h", - "Color": "#e4948e", - "Caption": "Week 4 after treatment with rifampicin", - "Symbol": "Circle" + "Color": "#c54a4a", + "Caption": "Treatment (with oral fluconazole)", + "Symbol": "Triangle" } ] }, { - "SectionId": 322, - "Title": "Shin 2013", - "SimulationDuration": 24, + "SectionId": 321, + "Title": "Olkkola 1996 Day 1", + "SimulationDuration": 7, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Shin 2013", + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_placebo_day 1", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Shin 2013 - Control phase (Midazolam alone) - Midazolam - IV - 1 mg - Plasma - agg. (n=24)", + "ObservedData": "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without Rifampicin)", + "Caption": "Control (without fluconazole)", "Symbol": "Circle" }, { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Shin 2013", + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 1", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Shin 2013 - CYP3A4 induced phase (Midazolam + rifampicin) - Midazolam - IV - 2.5 mg - Plasma - agg. (n=24)", - "StartTime": 216, + "ObservedData": "Olkkola 1996 - day 1 (po) with Perpetrator (Fluconazole) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", + "StartTime": 2, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with Rifampicin)", + "Caption": "Treatment (with fluconazole)", "Symbol": "Square" } ] }, { - "SectionId": 322, - "Title": "Shin 2016", - "SimulationDuration": 24, + "SectionId": 321, + "Title": "Olkkola 1996 Day 4", + "SimulationDuration": 7, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Shin 2016", + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_placebo_day 4", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Shin 2016 - Midazolam alone - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", + "ObservedData": "Olkkola 1996 - day 4 (iv) Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without Rifampicin)", + "Caption": "Control (without fluconazole)", "Symbol": "Circle" }, { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Shin 2016", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Shin 2016 - Midazolam + rifampicin - Midazolam - IV - 2.5 mg - Plasma - agg. (n=12)", - "StartTime": 216, + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 4", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Olkkola 1996 - day 4 (iv) with Perpetrator (Fluconazole) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)", + "StartTime": 74, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with Rifampicin)", + "Caption": "Treatment (with fluconazole)", "Symbol": "Square" } ] }, { - "SectionId": 322, - "Title": "Szalat 2007", - "SimulationDuration": 6, + "SectionId": 321, + "Title": "Olkkola 1996 Day 6", + "SimulationDuration": 17, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Szalat 2007", + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_placebo_day 6", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Szalat 2007 - Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)", + "ObservedData": "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without Rifampicin)", + "Caption": "Control (without fluconazole)", "Symbol": "Circle" }, { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Szalat 2007", + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 6", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Szalat 2007 - with Perpetrator (Rifampicin) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)", - "StartTime": 132, + "ObservedData": "Olkkola 1996 - day 6 (po) with Perpetrator (Fluconazole) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", + "StartTime": 122, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with Rifampicin)", + "Caption": "Treatment (with fluconazole)", "Symbol": "Square" } ] }, { "SectionId": 322, - "Title": "van Dyk 2018", - "SimulationDuration": 12, + "Title": "Varhe 1996c", + "SimulationDuration": 18, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - van Dyk 2018", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "van Dyk 2018 - Midazolam in Caucasian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=19)", + "Project": "Fluconazole-Triazolam-DDI", + "Simulation": "Varhe triazolam 0.25 mg po placebo", + "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Varhe 1996c - Triazolam + placebo - Triazolam - PO - 0.25 mg - Plasma - agg. (n=8)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without Rifampicin)", + "Caption": "Control (without fluconazole)", "Symbol": "Circle" }, { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - van Dyk 2018", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": [], - "StartTime": 156, + "Project": "Fluconazole-Triazolam-DDI", + "Simulation": "Varhe triazolam 0.25 mg po fluconazole 50mg", + "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Varhe 1996c - Triazolam with perpetrator fluconazole 50mg - Triazolam - PO - 0.25 mg - Plasma - agg. (n=8)", + "StartTime": 73, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with Rifampicin)", + "Caption": "Treatment (with 50 mg fluconazole)", "Symbol": "Square" + }, + { + "Project": "Fluconazole-Triazolam-DDI", + "Simulation": "Varhe triazolam 0.25 mg po fluconazole 100mg", + "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Varhe 1996c - Triazolam with perpetrator fluconazole 100mg - Triazolam - PO - 0.25 mg - Plasma - agg. (n=8)", + "StartTime": 73, + "TimeUnit": "h", + "Color": "#c54a4a", + "Caption": "Treatment (with 100 mg fluconazole)", + "Symbol": "Triangle" + }, + { + "Project": "Fluconazole-Triazolam-DDI", + "Simulation": "Varhe triazolam 0.25 mg po fluconazole 200mg", + "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Varhe 1996c - Triazolam with perpetrator fluconazole 200mg - Triazolam - PO - 0.25 mg - Plasma - agg. (n=8)", + "StartTime": 73, + "TimeUnit": "h", + "Color": "#d6706b", + "Caption": "Treatment (with 200 mg fluconazole)", + "Symbol": "Diamond" } ] }, { - "SectionId": 322, - "Title": "Wiesinger 2020", - "SimulationDuration": 24, + "SectionId": 301, + "Title": "Furukori 1998", + "SimulationDuration": 48, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Wiesinger 2020", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Wiesinger 2020 - Control phase (no RIF) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)", + "Project": "Carbamazepine-Alprazolam-DDI", + "Simulation": "Furukori1998_ControlPhase", + "Output": "Organism|PeripheralVenousBlood|Alprazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Furukori 1998 - treatment with placebo - Alprazolam - PO - 0.8 mg - Plasma - agg. (n=7)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without Rifampicin)", + "Caption": "Control (without carbamazepine)", "Symbol": "Circle" }, { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Wiesinger 2020", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Wiesinger 2020 - Weak-induction phase (RIF 10 mg) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)", - "StartTime": 180, - "TimeUnit": "h", - "Color": "#c54a4a", - "Caption": "Treatment (low dose 10 mg Rifampicin)", - "Symbol": "Triangle" - }, - { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Wiesinger 2020", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Wiesinger 2020 - Strong-induction phase (RIF 600 mg) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)", - "StartTime": 444, + "Project": "Carbamazepine-Alprazolam-DDI", + "Simulation": "Furukori1998_TreatmentPhase", + "Output": "Organism|PeripheralVenousBlood|Alprazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Furukori 1998 - treatment with carbamazepine - Alprazolam - PO - 0.8 mg - Plasma - agg. (n=7)", + "StartTime": 170, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (high dose 600 mg Rifampicin)", + "Caption": "Treatment (with carbamazepine)", "Symbol": "Square" } ] }, { - "SectionId": 322, - "Title": "Yu 2004 (CYP3A5*3/*3)", - "SimulationDuration": 15, + "SectionId": 303, + "Title": "Kanefendt 2023 (Study 1)", + "SimulationDuration": 24, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Control - Midazolam - Yu 2018 (CYP3A5 s3,s3)", + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Kanefendt2023_Study1_ControlPhase", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)", + "ObservedData": "Kanefendt 2023 - Study 1, midazolam alone - Midazolam - PO - 1 mg - Plasma - agg. (n=14)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without Rifampicin)", + "Caption": "Control (without carbamazepine)", "Symbol": "Circle" }, { - "Project": "Rifampicin-Midazolam-DDI", - "Simulation": "DDI Treatment - Rifampicin/Midazolam - Yu 2004 (CYP3A5 s3,s3)", + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Kanefendt2023_Study1_TreatmentPhase", "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Yu 2004 - Treatment Rifampicin CYP3A5*3/*3 - Midazolam - IV - 2 mg - Plasma - agg. (n=7)", - "StartTime": 240, + "ObservedData": "Kanefendt 2023 - Study 1, midazolam after pretreatment with carbamazepine - Midazolam - PO - 1 mg - Plasma - agg. (n=14)", + "StartTime": 334, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with Rifampicin)", + "Caption": "Treatment (with carbamazepine)", "Symbol": "Square" } ] }, { - "SectionId": 323, - "Title": "Villikka 1997", - "SimulationDuration": 12, + "SectionId": 303, + "Title": "Kanefendt 2023 (Study 2)", + "SimulationDuration": 24, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Rifampicin-Triazolam-DDI", - "Simulation": "Villikka 1997 - Triazolam control - 0.5 mg SD PO", - "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Villikka 1997 - Triazolam + placebo - Triazolam - PO - 0.5 mg - Plasma - agg. (n=10)", + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Kanefendt2023_Study2_ControlPhase", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kanefendt 2023 - Study 2, midazolam alone - Midazolam - PO - 1 mg - Plasma - agg. (n=13)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without Rifampicin)", + "Caption": "Control (without carbamazepine)", "Symbol": "Circle" }, { - "Project": "Rifampicin-Triazolam-DDI", - "Simulation": "Villikka 1997 - Rifampicin 600 mg over 5 days and Triazolam 0.5 mg SD PO", - "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Villikka 1997 - Treatment arm (pretreatment with rifampin; 600 mg; 5 days) - Triazolam - PO - 0.5 mg - Plasma - agg. (n=10)", - "StartTime": 113, + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Kanefendt2023_Study2_TreatmentPhase", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "Kanefendt 2023 - Study 2, midazolam after pretreatment with carbamazepine - Midazolam - PO - 1 mg - Plasma - agg. (n=13)", + "StartTime": 336, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment with Rifampicin", + "Caption": "Treatment (with carbamazepine)", "Symbol": "Square" } ] }, { - "SectionId": 324, - "Title": "Barbarash 1988 (verapamil IV)", - "SimulationDuration": 15, + "SectionId": 303, + "Title": "Lutz 2018", + "SimulationDuration": 24, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Rifampicin-Verapamil-DDI", - "Simulation": "DDI Control - Verapamil - Barbarash 1988 (iv)", - "Output": "Organism|PeripheralVenousBlood|Verapamil|Plasma (Peripheral Venous Blood)", - "ObservedData": "Barbarash 1988 - Verapamil IV control - Verapamil - IV - 10 mg - Serum - agg. (n=6)", + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Lutz2018_ControlPhase", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": [], "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without Rifampicin)", + "Caption": "Control (without carbamazepine)", "Symbol": "Circle" }, { - "Project": "Rifampicin-Verapamil-DDI", - "Simulation": "DDI Treatment - Rifampicin/Verapamil - Barbarash 1988 (iv)", - "Output": "Organism|PeripheralVenousBlood|Verapamil|Plasma (Peripheral Venous Blood)", - "ObservedData": "Barbarash 1988 - Verapamil IV after 2 weeks of Rifampicin therapy - Verapamil - IV - 10 mg - Serum - agg. (n=6)", - "StartTime": 300, + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Lutz2018_TreatmentPhase", + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": [], + "StartTime": 576, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment with Rifampicin", + "Caption": "Treatment (with carbamazepine)", "Symbol": "Square" } ] }, { - "SectionId": 324, - "Title": "Barbarash 1988 (verapamil PO)", - "SimulationDuration": 15, + "SectionId": 302, + "Title": "Ji 2008 (Arm 1, Perpetrator: Carbamazepine, Victim: Efavirenz)", + "SimulationDuration": 24, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Rifampicin-Verapamil-DDI", - "Simulation": "DDI Control - Verapamil - Barbarash 1988 (po)", - "Output": "Organism|PeripheralVenousBlood|Verapamil|Plasma (Peripheral Venous Blood)", - "ObservedData": "Barbarash 1988 - Verapamil PO control - Verapamil - PO - 120 mg - Serum - agg. (n=6)", - "StartTime": 0, + "Project": "Carbamazepine-Efavirenz-DDI", + "Simulation": "Ji2008_Arm1_ControlPhase", + "Output": "Organism|PeripheralVenousBlood|Efavirenz|Plasma (Peripheral Venous Blood)", + "ObservedData": "Ji 2008 - Efavirenz, control (Arm 1) - Efavirenz - PO - 600 mg - Plasma - agg. (n=14)", + "StartTime": 312, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without Rifampicin)", + "Caption": "Control (without carbamazepine)", "Symbol": "Circle" }, { - "Project": "Rifampicin-Verapamil-DDI", - "Simulation": "DDI Treatment - Rifampicin/Verapamil - Barbarash 1988 (po)", - "Output": "Organism|PeripheralVenousBlood|Verapamil|Plasma (Peripheral Venous Blood)", - "ObservedData": "Barbarash 1988 - Verapamil PO after 2 weeks of Rifampicin therapy - Verapamil - PO - 120 mg - Serum - agg. (n=6)", - "StartTime": 348, + "Project": "Carbamazepine-Efavirenz-DDI", + "Simulation": "Ji2008_Arm1_TreatmentPhase", + "Output": "Organism|PeripheralVenousBlood|Efavirenz|Plasma (Peripheral Venous Blood)", + "ObservedData": "Ji 2008 - Efavirenz + Carbamazepine, treatment (Arm 1) - Efavirenz - PO - 600 mg - Plasma - agg. (n=14)", + "StartTime": 816, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment with Rifampicin", + "Caption": "Treatment (with carbamazepine)", "Symbol": "Square" } ] }, { - "SectionId": 325, - "Title": "Palkama 1998", - "SimulationDuration": 10, + "SectionId": 317, + "Title": "Barzaghi 1987", + "SimulationDuration": 96, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Fluconazole-Alfentanil-DDI", - "Simulation": "Alfentanil placebo", - "Output": "Organism|PeripheralVenousBlood|Alfentanil|Plasma (Peripheral Venous Blood)", - "ObservedData": "Palkama 1998 - Alfentanil placebo - Alfentanil - IV - 20 µg/kg - Plasma - agg. (n=9)", - "StartTime": 1, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Barzaghi1987_ControlPhase", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "Barzaghi 1987 - Without erythromycin - Carbamazepine - PO - 400 mg - Serum - agg. (n=7)", + "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without fluconazole)", + "Caption": "Control (without carbamazepine)", "Symbol": "Circle" }, { - "Project": "Fluconazole-Alfentanil-DDI", - "Simulation": "Alfentanil -Fluconzole i.v. DDI", - "Output": "Organism|PeripheralVenousBlood|Alfentanil|Plasma (Peripheral Venous Blood)", - "ObservedData": "Palkama 1998 - Alfentanil with perpetrator fluconazole i.v. - Alfentanil - IV - 20 µg/kg - Plasma - agg. (n=9)", - "StartTime": 1, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Barzaghi1987_TreatmentPhase", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "Barzaghi 1987 - With erythromycin - Carbamazepine - PO - 400 mg - Serum - agg. (n=7)", + "StartTime": 144, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with intravenous fluconazole)", + "Caption": "Treatment (with carbamazepine)", "Symbol": "Square" - }, - { - "Project": "Fluconazole-Alfentanil-DDI", - "Simulation": "Alfentanil -Fluconzole oral. DDI", - "Output": "Organism|PeripheralVenousBlood|Alfentanil|Plasma (Peripheral Venous Blood)", - "ObservedData": "Palkama 1998 - Alfentanil with perpetrator fluconazole po - Alfentanil - IV - 20 µg/kg - Plasma - agg. (n=9)", - "StartTime": 1, - "TimeUnit": "h", - "Color": "#c54a4a", - "Caption": "Treatment (with oral fluconazole)", - "Symbol": "Triangle" } ] }, { - "SectionId": 326, - "Title": "Ahonen 1997", - "SimulationDuration": 17, + "SectionId": 317, + "Title": "Wong 1983", + "SimulationDuration": 72, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Ahonen_midazolam_po_7.5mg_placebo", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Ahonen 1997 - Midazolam placebo - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)", - "StartTime": 1, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Wong1983_ControlPhase", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "Wong 1983 - Treatment B (without erythromycin) - Carbamazepine - PO - 400 mg - Plasma - indiv.", + "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without fluconazole)", + "Caption": "Control (without carbamazepine)", "Symbol": "Circle" }, { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Ahonen_midazolam_po_7.5mg_fluconazole_400mg_i.v_DDI", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Ahonen 1997 - Midazolam with perpetrator fluconazole i.v - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)", - "StartTime": 1, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Wong1983_TreatmentPhase", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "Wong 1983 - Treatment A (with erythromycin) - Carbamazepine - PO - 400 mg - Plasma - indiv.", + "StartTime": 120, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with intravenous fluconazole)", + "Caption": "Treatment (with carbamazepine)", "Symbol": "Square" - }, - { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Ahonen_midazolam_po_7.5mg_fluconazole_400mg_po_DDI", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Ahonen 1997 - Midazolam with perpetrator fluconazole oral - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)", - "StartTime": 1, - "TimeUnit": "h", - "Color": "#c54a4a", - "Caption": "Treatment (with oral fluconazole)", - "Symbol": "Triangle" } ] }, { - "SectionId": 326, - "Title": "Olkkola 1996 Day 1", - "SimulationDuration": 7, + "SectionId": 317, + "Title": "Miles 1989 (average dose of 357 mg)", + "SimulationDuration": 24, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_placebo_day 1", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", - "StartTime": 0, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Miles1989_ControlPhase_357mg", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "Miles 1989 - CBZ before ERY - Carbamazepine - PO - 300-400; mean dose: 357.1 +/- 53.5 mg - Serum - agg. (n=7)", + "StartTime": 312, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without fluconazole)", - "Symbol": "Circle" - }, - { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 1", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Olkkola 1996 - day 1 (po) with Perpetrator (Fluconazole) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", - "StartTime": 2, + "Caption": "Control (without carbamazepine)", + "Symbol": "Circle" + }, + { + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Miles1989_TreatmentPhase_357mg", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "Miles 1989 - CBZ during ERY - Carbamazepine - PO - 300-400; mean dose: 357.1 +/- 53.5 mg - Serum - agg. (n=7)", + "StartTime": 384, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with fluconazole)", + "Caption": "Treatment (with carbamazepine)", "Symbol": "Square" } ] }, { - "SectionId": 326, - "Title": "Olkkola 1996 Day 4", - "SimulationDuration": 7, + "SectionId": 317, + "Title": "Miles 1989 (300 mg)", + "SimulationDuration": 24, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_placebo_day 4", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Olkkola 1996 - day 4 (iv) Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)", - "StartTime": 0, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Miles1989_ControlPhase_300mg", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": [], + "StartTime": 312, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without fluconazole)", + "Caption": "Control (without carbamazepine)", "Symbol": "Circle" }, { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 4", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Olkkola 1996 - day 4 (iv) with Perpetrator (Fluconazole) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)", - "StartTime": 74, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Miles1989_TreatmentPhase_300mg", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": [], + "StartTime": 384, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with fluconazole)", + "Caption": "Treatment (with carbamazepine)", "Symbol": "Square" } ] }, { - "SectionId": 326, - "Title": "Olkkola 1996 Day 6", - "SimulationDuration": 17, + "SectionId": 317, + "Title": "Miles 1989 (400 mg)", + "SimulationDuration": 24, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_placebo_day 6", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", - "StartTime": 0, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Miles1989_ControlPhase_400mg", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": [], + "StartTime": 312, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without fluconazole)", + "Caption": "Control (without carbamazepine)", "Symbol": "Circle" }, { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 6", - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Olkkola 1996 - day 6 (po) with Perpetrator (Fluconazole) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", - "StartTime": 122, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Miles1989_TreatmentPhase_400mg", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": [], + "StartTime": 384, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with fluconazole)", + "Caption": "Treatment (with carbamazepine)", "Symbol": "Square" } ] }, { - "SectionId": 327, - "Title": "Varhe 1996c", - "SimulationDuration": 18, + "SectionId": 306, + "Title": "Dalton 1985a", + "SimulationDuration": 154, "TimeUnit": "h", "OutputMappings": [ { - "Project": "Fluconazole-Triazolam-DDI", - "Simulation": "Varhe triazolam 0.25 mg po placebo", - "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Varhe 1996c - Triazolam + placebo - Triazolam - PO - 0.25 mg - Plasma - agg. (n=8)", + "Project": "Cimetidine-Carbamazepine-DDI", + "Simulation": "Dalton1985a_ControlPhase", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "Dalton 1985a - Placebo (without cimetidine) - Carbamazepine - PO - 600 mg - Plasma - agg. (n=8)", "StartTime": 0, "TimeUnit": "h", "Color": "#2166ac", - "Caption": "Control (without fluconazole)", + "Caption": "Control (without cimetidine)", "Symbol": "Circle" }, { - "Project": "Fluconazole-Triazolam-DDI", - "Simulation": "Varhe triazolam 0.25 mg po fluconazole 50mg", - "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Varhe 1996c - Triazolam with perpetrator fluconazole 50mg - Triazolam - PO - 0.25 mg - Plasma - agg. (n=8)", - "StartTime": 73, + "Project": "Cimetidine-Carbamazepine-DDI", + "Simulation": "Dalton1985a_TreatmentPhase", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": [], + "StartTime": 47, "TimeUnit": "h", "Color": "#b2182b", - "Caption": "Treatment (with 50 mg fluconazole)", + "Caption": "Treatment (with cimetidine)", "Symbol": "Square" - }, + } + ] + }, + { + "SectionId": 313, + "Title": "Ji 2008 (Arm 2, Perpetrator: Efavirenz, Victim: Carbamazepine)", + "SimulationDuration": 24, + "TimeUnit": "h", + "OutputMappings": [ { - "Project": "Fluconazole-Triazolam-DDI", - "Simulation": "Varhe triazolam 0.25 mg po fluconazole 100mg", - "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Varhe 1996c - Triazolam with perpetrator fluconazole 100mg - Triazolam - PO - 0.25 mg - Plasma - agg. (n=8)", - "StartTime": 73, + "Project": "Efavirenz-Carbamazepine-DDI", + "Simulation": "Ji2008_Arm2_ControlPhase", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "Ji 2008 - Carbamazepine, control (Arm 2) - Carbamazepine - PO - 200 / 400 mg - Plasma - agg. (n=36)", + "StartTime": 480, "TimeUnit": "h", - "Color": "#c54a4a", - "Caption": "Treatment (with 100 mg fluconazole)", - "Symbol": "Triangle" + "Color": "#2166ac", + "Caption": "Control (without efavirenz)", + "Symbol": "Circle" }, { - "Project": "Fluconazole-Triazolam-DDI", - "Simulation": "Varhe triazolam 0.25 mg po fluconazole 200mg", - "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", - "ObservedData": "Varhe 1996c - Triazolam with perpetrator fluconazole 200mg - Triazolam - PO - 0.25 mg - Plasma - agg. (n=8)", - "StartTime": 73, + "Project": "Efavirenz-Carbamazepine-DDI", + "Simulation": "Ji2008_Arm2_TreatmentPhase", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "Ji 2008 - Carbamazepine + Efavirenz, treatment (Arm 2) - Carbamazepine - PO - 200 / 400 mg - Plasma - agg. (n=36)", + "StartTime": 816, "TimeUnit": "h", - "Color": "#d6706b", - "Caption": "Treatment (with 200 mg fluconazole)", - "Symbol": "Diamond" + "Color": "#b2182b", + "Caption": "Treatment (with efavirenz)", + "Symbol": "Square" } ] } @@ -17155,147 +18205,398 @@ { "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "DDI Ratios", - "ObservedDataRecordId": 1393, + "ObservedDataRecordId": 1393, + "SimulationControl": { + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Ahonen_midazolam_po_7.5mg_placebo", + "StartTime": 1, + "EndTime": 8, + "TimeUnit": "h" + }, + "SimulationDDI": { + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Ahonen_midazolam_po_7.5mg_fluconazole_400mg_po_DDI", + "StartTime": 1, + "EndTime": 8, + "TimeUnit": "h" + } + }, + { + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "DDI Ratios", + "ObservedDataRecordId": 380, + "SimulationControl": { + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_placebo_day 1", + "StartTime": 0, + "EndTime": 7, + "TimeUnit": "h" + }, + "SimulationDDI": { + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 1", + "StartTime": 0, + "EndTime": 7, + "TimeUnit": "h" + } + }, + { + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "DDI Ratios", + "ObservedDataRecordId": 382, + "SimulationControl": { + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_placebo_day 6", + "StartTime": 0, + "EndTime": 17, + "TimeUnit": "h" + }, + "SimulationDDI": { + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 6", + "StartTime": 122, + "EndTime": 139, + "TimeUnit": "h" + } + } + ] + }, + { + "Caption": "Fluconazole + Midazolam (iv)", + "Color": "#01665e", + "Symbol": "Square", + "DDIRatios": [ + { + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "DDI Ratios", + "ObservedDataRecordId": 381, + "SimulationControl": { + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_placebo_day 4", + "StartTime": 0, + "EndTime": 7, + "TimeUnit": "h" + }, + "SimulationDDI": { + "Project": "Fluconazole-Midazolam-DDI", + "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 4", + "StartTime": 74, + "EndTime": 91, + "TimeUnit": "h" + } + } + ] + }, + { + "Caption": "Fluconazole + Triazolam (po)", + "Color": "#dfc27d", + "Symbol": "Circle", + "DDIRatios": [ + { + "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "DDI Ratios", + "ObservedDataRecordId": 1394, + "SimulationControl": { + "Project": "Fluconazole-Triazolam-DDI", + "Simulation": "Varhe triazolam 0.25 mg po placebo", + "StartTime": 0, + "EndTime": 18, + "TimeUnit": "h" + }, + "SimulationDDI": { + "Project": "Fluconazole-Triazolam-DDI", + "Simulation": "Varhe triazolam 0.25 mg po fluconazole 50mg", + "StartTime": 73, + "EndTime": 91, + "TimeUnit": "h" + } + }, + { + "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "DDI Ratios", + "ObservedDataRecordId": 1395, + "SimulationControl": { + "Project": "Fluconazole-Triazolam-DDI", + "Simulation": "Varhe triazolam 0.25 mg po placebo", + "StartTime": 0, + "EndTime": 18, + "TimeUnit": "h" + }, + "SimulationDDI": { + "Project": "Fluconazole-Triazolam-DDI", + "Simulation": "Varhe triazolam 0.25 mg po fluconazole 100mg", + "StartTime": 73, + "EndTime": 91, + "TimeUnit": "h" + } + }, + { + "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "DDI Ratios", + "ObservedDataRecordId": 1396, + "SimulationControl": { + "Project": "Fluconazole-Triazolam-DDI", + "Simulation": "Varhe triazolam 0.25 mg po placebo", + "StartTime": 0, + "EndTime": 18, + "TimeUnit": "h" + }, + "SimulationDDI": { + "Project": "Fluconazole-Triazolam-DDI", + "Simulation": "Varhe triazolam 0.25 mg po fluconazole 200mg", + "StartTime": 73, + "EndTime": 91, + "TimeUnit": "h" + } + } + ] + }, + { + "Caption": "Carbamazepine + Alprazolam (po)", + "Color": "#FF5050", + "Symbol": "Circle", + "DDIRatios": [ + { + "Output": "Organism|PeripheralVenousBlood|Alprazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "DDI Ratios", + "ObservedDataRecordId": 1457, + "SimulationControl": { + "Project": "Carbamazepine-Alprazolam-DDI", + "Simulation": "Furukori1998_ControlPhase", + "StartTime": 0, + "EndTime": "Inf", + "TimeUnit": "h" + }, + "SimulationDDI": { + "Project": "Carbamazepine-Alprazolam-DDI", + "Simulation": "Furukori1998_TreatmentPhase", + "StartTime": 170, + "EndTime": "Inf", + "TimeUnit": "h" + } + } + ] + }, + { + "Caption": "Carbamazepine + Midazolam (po)", + "Color": "#5C0000", + "Symbol": "Circle", + "DDIRatios": [ + { + "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "ObservedData": "DDI Ratios", + "ObservedDataRecordId": 943, "SimulationControl": { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Ahonen_midazolam_po_7.5mg_placebo", - "StartTime": 1, - "EndTime": 8, + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Kanefendt2023_Study1_ControlPhase", + "StartTime": 0, + "EndTime": "Inf", "TimeUnit": "h" }, "SimulationDDI": { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Ahonen_midazolam_po_7.5mg_fluconazole_400mg_po_DDI", - "StartTime": 1, - "EndTime": 8, + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Kanefendt2023_Study1_TreatmentPhase", + "StartTime": 334, + "EndTime": "Inf", "TimeUnit": "h" } }, { "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "DDI Ratios", - "ObservedDataRecordId": 380, + "ObservedDataRecordId": 1133, "SimulationControl": { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_placebo_day 1", + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Kanefendt2023_Study2_ControlPhase", "StartTime": 0, - "EndTime": 7, + "EndTime": "Inf", "TimeUnit": "h" }, "SimulationDDI": { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 1", - "StartTime": 0, - "EndTime": 7, + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Kanefendt2023_Study2_TreatmentPhase", + "StartTime": 336, + "EndTime": "Inf", "TimeUnit": "h" } }, { "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "DDI Ratios", - "ObservedDataRecordId": 382, + "ObservedDataRecordId": 1460, "SimulationControl": { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_placebo_day 6", + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Lutz2018_ControlPhase", "StartTime": 0, - "EndTime": 17, + "EndTime": "Inf", "TimeUnit": "h" }, "SimulationDDI": { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 6", - "StartTime": 122, - "EndTime": 139, + "Project": "Carbamazepine-Midazolam-DDI", + "Simulation": "Lutz2018_TreatmentPhase", + "StartTime": 404, + "EndTime": "Inf", "TimeUnit": "h" } } ] }, { - "Caption": "Fluconazole + Midazolam (iv)", - "Color": "#01665e", - "Symbol": "Square", + "Caption": "Carbamazepine + Efavirenz (po)", + "Color": "#B06900", + "Symbol": "Circle", "DDIRatios": [ { - "Output": "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", + "Output": "Organism|PeripheralVenousBlood|Efavirenz|Plasma (Peripheral Venous Blood)", "ObservedData": "DDI Ratios", - "ObservedDataRecordId": 381, + "ObservedDataRecordId": 959, "SimulationControl": { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_placebo_day 4", - "StartTime": 0, - "EndTime": 7, + "Project": "Carbamazepine-Efavirenz-DDI", + "Simulation": "Ji2008_Arm1_ControlPhase", + "StartTime": 312, + "EndTime": 336, "TimeUnit": "h" }, "SimulationDDI": { - "Project": "Fluconazole-Midazolam-DDI", - "Simulation": "Olkkola_midazolam_fluconazole_DDI_day 4", - "StartTime": 74, - "EndTime": 91, + "Project": "Carbamazepine-Efavirenz-DDI", + "Simulation": "Ji2008_Arm1_TreatmentPhase", + "StartTime": 816, + "EndTime": 840, "TimeUnit": "h" } } ] }, { - "Caption": "Fluconazole + Triazolam (po)", - "Color": "#dfc27d", + "Caption": "Erythromycin + Carbamazepine (po)", + "Color": "#7030A0", "Symbol": "Circle", "DDIRatios": [ { - "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", "ObservedData": "DDI Ratios", - "ObservedDataRecordId": 1394, + "ObservedDataRecordId": 465, "SimulationControl": { - "Project": "Fluconazole-Triazolam-DDI", - "Simulation": "Varhe triazolam 0.25 mg po placebo", + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Barzaghi1987_ControlPhase", "StartTime": 0, - "EndTime": 18, + "EndTime": "Inf", "TimeUnit": "h" }, "SimulationDDI": { - "Project": "Fluconazole-Triazolam-DDI", - "Simulation": "Varhe triazolam 0.25 mg po fluconazole 50mg", - "StartTime": 73, - "EndTime": 91, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Barzaghi1987_TreatmentPhase", + "StartTime": 144, + "EndTime": "Inf", "TimeUnit": "h" } }, { - "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", "ObservedData": "DDI Ratios", - "ObservedDataRecordId": 1395, + "ObservedDataRecordId": 1157, "SimulationControl": { - "Project": "Fluconazole-Triazolam-DDI", - "Simulation": "Varhe triazolam 0.25 mg po placebo", - "StartTime": 0, - "EndTime": 18, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Miles1989_ControlPhase_300mg", + "StartTime": 312, + "EndTime": 336, "TimeUnit": "h" }, "SimulationDDI": { - "Project": "Fluconazole-Triazolam-DDI", - "Simulation": "Varhe triazolam 0.25 mg po fluconazole 100mg", - "StartTime": 73, - "EndTime": 91, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Miles1989_TreatmentPhase_300mg", + "StartTime": 384, + "EndTime": 408, "TimeUnit": "h" } }, { - "Output": "Organism|PeripheralVenousBlood|Triazolam|Plasma (Peripheral Venous Blood)", + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", "ObservedData": "DDI Ratios", - "ObservedDataRecordId": 1396, + "ObservedDataRecordId": 1158, "SimulationControl": { - "Project": "Fluconazole-Triazolam-DDI", - "Simulation": "Varhe triazolam 0.25 mg po placebo", + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Miles1989_ControlPhase_400mg", + "StartTime": 312, + "EndTime": 336, + "TimeUnit": "h" + }, + "SimulationDDI": { + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Miles1989_TreatmentPhase_400mg", + "StartTime": 384, + "EndTime": 408, + "TimeUnit": "h" + } + }, + { + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "DDI Ratios", + "ObservedDataRecordId": 1154, + "SimulationControl": { + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Wong1983_ControlPhase", "StartTime": 0, - "EndTime": 18, + "EndTime": "Inf", "TimeUnit": "h" }, "SimulationDDI": { - "Project": "Fluconazole-Triazolam-DDI", - "Simulation": "Varhe triazolam 0.25 mg po fluconazole 200mg", - "StartTime": 73, - "EndTime": 91, + "Project": "Erythromycin-Carbamazepine-DDI", + "Simulation": "Wong1983_TreatmentPhase", + "StartTime": 120, + "EndTime": "Inf", + "TimeUnit": "h" + } + } + ] + }, + { + "Caption": "Cimetidine + Carbamazepine (po)", + "Color": "#9BC2E6", + "Symbol": "Circle", + "DDIRatios": [ + { + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "DDI Ratios", + "ObservedDataRecordId": 900, + "SimulationControl": { + "Project": "Cimetidine-Carbamazepine-DDI", + "Simulation": "Dalton1985a_ControlPhase", + "StartTime": 0, + "EndTime": "Inf", + "TimeUnit": "h" + }, + "SimulationDDI": { + "Project": "Cimetidine-Carbamazepine-DDI", + "Simulation": "Dalton1985a_TreatmentPhase", + "StartTime": 48, + "EndTime": "Inf", + "TimeUnit": "h" + } + } + ] + }, + { + "Caption": "Efavirenz + Carbamazepine (po)", + "Color": "#B4B4B4", + "Symbol": "Circle", + "DDIRatios": [ + { + "Output": "Organism|PeripheralVenousBlood|Carbamazepine|Plasma (Peripheral Venous Blood)", + "ObservedData": "DDI Ratios", + "ObservedDataRecordId": 961, + "SimulationControl": { + "Project": "Efavirenz-Carbamazepine-DDI", + "Simulation": "Ji2008_Arm2_ControlPhase", + "StartTime": 480, + "EndTime": 504, + "TimeUnit": "h" + }, + "SimulationDDI": { + "Project": "Efavirenz-Carbamazepine-DDI", + "Simulation": "Ji2008_Arm2_TreatmentPhase", + "StartTime": 816, + "EndTime": 840, "TimeUnit": "h" } } @@ -17324,138 +18625,168 @@ "Sections": [ { "Id": 1201, + "Title": "Carbamazepine - Alprazolam DDI", + "Content": "Content/Carbamazepine-Alprazolam-DDI.md" + }, + { + "Id": 1202, + "Title": "Carbamazepine - Efavirenz DDI", + "Content": "Content/Carbamazepine-Efavirenz-DDI.md" + }, + { + "Id": 1203, + "Title": "Carbamazepine - Midazolam DDI", + "Content": "Content/Carbamazepine-Midazolam-DDI.md" + }, + { + "Id": 1204, "Title": "Cimetidine - Alfentanil DDI", "Content": "Content/Cimetidine-Alfentanil-DDI.md" }, { - "Id": 1202, + "Id": 1205, "Title": "Cimetidine - Alprazolam DDI", "Content": "Content/Cimetidine-Alprazolam-DDI.md" }, { - "Id": 1203, + "Id": 1206, + "Title": "Cimetidine - Carbamazepine DDI", + "Content": "Content/Cimetidine-Carbamazepine-DDI.md" + }, + { + "Id": 1207, "Title": "Cimetidine - Midazolam DDI", "Content": "Content/Cimetidine-Midazolam-DDI.md" }, { - "Id": 1204, + "Id": 1208, "Title": "Cimetidine - Triazolam DDI", "Content": "Content/Cimetidine-Triazolam-DDI.md" }, { - "Id": 1205, + "Id": 1209, "Title": "Cimetidine - Verapamil DDI", "Content": "Content/Cimetidine-Verapamil-DDI.md" }, { - "Id": 1206, + "Id": 1210, "Title": "Clarithromycin - Midazolam DDI", "Content": "Content/Clarithromycin-Midazolam-DDI.md" }, { - "Id": 1207, + "Id": 1211, "Title": "Clarithromycin - Triazolam DDI", "Content": "Content/Clarithromycin-Triazolam-DDI.md" }, { - "Id": 1208, + "Id": 1212, + "Title": "Efavirenz - Alfentanil-DDI", + "Content": "Content/Efavirenz-Alfentanil-DDI.md" + }, + { + "Id": 1213, + "Title": "Efavirenz - Carbamazepine DDI", + "Content": "Content/Efavirenz-Carbamazepine-DDI.md" + }, + { + "Id": 1214, + "Title": "Efavirenz - Midazolam DDI", + "Content": "Content/Efavirenz-Midazolam-DDI.md" + }, + { + "Id": 1215, "Title": "Erythromycin - Alfentanil DDI", "Content": "Content/Erythromycin-Alfentanil-DDI.md" }, { - "Id": 1209, + "Id": 1216, "Title": "Erythromycin - Alprazolam DDI", "Content": "Content/Erythromycin-Alprazolam-DDI.md" }, { - "Id": 1210, + "Id": 1217, + "Title": "Erythromycin - Carbamazepine DDI", + "Content": "Content/Erythromycin-Carbamazepine-DDI.md" + }, + { + "Id": 1218, "Title": "Erythromycin - Midazolam DDI", "Content": "Content/Erythromycin-Midazolam-DDI.md" }, { - "Id": 1211, + "Id": 1219, "Title": "Erythromycin - Triazolam DDI", "Content": "Content/Erythromycin-Triazolam-DDI.md" }, { - "Id": 1212, + "Id": 1220, + "Title": "Fluconazole - Alfentanil DDI", + "Content": "Content/Fluconazole-Alfentanil-DDI.md" + }, + { + "Id": 1221, + "Title": "Fluconazole - Midazolam DDI", + "Content": "Content/Fluconazole-Midazolam-DDI.md" + }, + { + "Id": 1222, + "Title": "Fluconazole - Triazolam DDI", + "Content": "Content/Fluconazole-Triazolam-DDI.md" + }, + { + "Id": 1223, "Title": "Fluvoxamine - Alprazolam DDI", "Content": "Content/Fluvoxamine-Alprazolam-DDI.md" }, { - "Id": 1213, + "Id": 1224, "Title": "Fluvoxamine - Midazolam DDI", "Content": "Content/Fluvoxamine-Midazolam-DDI.md" }, { - "Id": 1214, + "Id": 1225, "Title": "Itraconazole - Alprazolam DDI", "Content": "Content/Itraconazole-Alprazolam-DDI.md" }, { - "Id": 1215, + "Id": 1226, "Title": "Itraconazole - Midazolam DDI", "Content": "Content/Itraconazole-Midazolam-DDI.md" }, { - "Id": 1216, + "Id": 1227, "Title": "Itraconazole - Triazolam DDI", "Content": "Content/Itraconazole-Triazolam-DDI.md" }, { - "Id": 1217, - "Title": "Verapamil - Midazolam DDI", - "Content": "Content/Verapamil-Midazolam-DDI.md" - }, - { - "Id": 1218, - "Title": "Efavirenz - Alfentanil-DDI", - "Content": "Content/Efavirenz-Alfentanil-DDI.md" - }, - { - "Id": 1219, - "Title": "Efavirenz - Midazolam DDI", - "Content": "Content/Efavirenz-Midazolam-DDI.md" - }, - { - "Id": 1220, + "Id": 1228, "Title": "Rifampicin - Alfentanil DDI", "Content": "Content/Rifampicin-Alfentanil-DDI.md" }, { - "Id": 1221, + "Id": 1229, "Title": "Rifampicin - Alprazolam DDI", "Content": "Content/Rifampicin-Alprazolam-DDI.md" }, { - "Id": 1222, + "Id": 1230, "Title": "Rifampicin - Midazolam DDI", "Content": "Content/Rifampicin-Midazolam-DDI.md" }, { - "Id": 1223, + "Id": 1231, "Title": "Rifampicin - Triazolam DDI", "Content": "Content/Rifampicin-Triazolam-DDI.md" }, { - "Id": 1224, + "Id": 1232, "Title": "Rifampicin - Verapamil DDI", "Content": "Content/Rifampicin-Verapamil-DDI.md" - }, - { - "Id": 1225, - "Title": "Fluconazole - Alfentanil DDI", - "Content": "Content/Fluconazole-Alfentanil-DDI.md" - }, - { - "Id": 1226, - "Title": "Fluconazole - Midazolam DDI", - "Content": "Content/Fluconazole-Midazolam-DDI.md" }, { - "Id": 1227, - "Title": "Fluconazole - Triazolam DDI", - "Content": "Content/Fluconazole-Triazolam-DDI.md" + "Id": 1233, + "Title": "Verapamil - Midazolam DDI", + "Content": "Content/Verapamil-Midazolam-DDI.md" } ] } @@ -17473,137 +18804,167 @@ "Sections": [ { "Id": 301, - "Title": "3.1 Cimetidine - Alfentanil DDI", + "Title": "3.1 Carbamazepine - 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