Open-Systems-Pharmacology · Yuri05 · Feb 7, 2024 · May 23, 2022 · May 23, 2022 · May 23, 2022
diff --git 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
@@ -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<br />Alprazolam: 0.8 mg po single dose, 2 hours after the 22<sup>nd</sup> carbamazepine dose | [Furukori 1998](#4-references) |
diff --git a/Qualification/Input/Content/Carbamazepine-Efavirenz-DDI.md 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:<br />Carbamazepine (starting with the 15<sup>th</sup> 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<br />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
@@ -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<br />Midazolam: 2 mg po single dose, concomitantly with the 49<sup>th</sup> 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<br />Midazolam: 1 mg po single dose, 10 hours after the 26<sup>th</sup> 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<br />Midazolam: 1 mg po single dose, 12 hours after the 28<sup>th</sup> carbamazepine dose         | [Kanefendt 2023](#4-references) |
diff --git a/Qualification/Input/Content/Cimetidine-Carbamazepine-DDI.md 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<br />Carbamazepine: 600 mg po single dose, one hour before the 9<sup>th</sup> 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
@@ -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:<br />Efavirenz (starting with the 25<sup>th</sup> dose of carbamazepine): 600 mg po QD for 14 days<br />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
@@ -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<br />Carbamazepine: 400 mg po single dose, administered on the 7<sup>th</sup> 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<br />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<br />Carbamazepine: 400 mg po QD for 17 days                  | [Miles 1989](#4-references)    |
+| 1154   | CYP3A4 | Erythromycin / carbamazepine | Erythromycin: 250 mg po QID for 8 days<br />Carbamazepine: 400 mg po single dose, administered on the 6<sup>th</sup> 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
@@ -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)
 
 <sub>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.</sub>
 
-
-
 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).
-