Fluvoxamine-Voriconazole-Bupropion-DDI.json

{
  "Version": 77,
  "Individuals": [
    {
      "Name": "Bosilkovska 2014 (n=10)",
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  "Compounds": [
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      "Name": "Bupropion",
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      "PlasmaProteinBindingPartner": "Albumin",
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      "FractionUnbound": [
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              "ValueOrigin": {
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                "Description": "Reese 2018"
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        {
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        {
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        {
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                "Description": "Wang 2020 ((Vmax1* CL1 + Vmax2*CL2)/(Cl1+Cl2))"
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              "ValueOrigin": {
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        {
          "InternalName": "rCYP450_MM",
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            {
              "Name": "In vitro Vmax/recombinant enzyme",
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              "Unit": "pmol/min/pmol rec. enzyme",
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                "Source": "Publication",
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            },
            {
              "Name": "Km",
              "Value": 15.59,
              "Unit": "µmol/l",
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                "Source": "Publication",
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                "Description": " Wang 2020 ((Km1* CL1 + Km2*CL2)/(Cl1+Cl2))"
              }
            }
          ]
        },
        {
          "InternalName": "MetabolizationLiverMicrosomes_MM",
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          "Metabolite": "Hydroxybupropion",
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            {
              "Name": "In vitro Vmax for liver microsomes",
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              "Unit": "pmol/min/mg mic. protein",
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            },
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                "Description": "Xu 2012 (corrected with microsomal fu)"
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            },
            {
              "Name": "kcat",
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              "Unit": "1/min",
              "ValueOrigin": {
                "Source": "ParameterIdentification",
                "Method": "ParameterIdentification"
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            }
          ]
        },
        {
          "InternalName": "MetabolizationLiverMicrosomes_MM",
          "DataSource": "PM (*6 l *6)",
          "Molecule": "CYP2B6",
          "Metabolite": "Hydroxybupropion",
          "Parameters": [
            {
              "Name": "In vitro Vmax for liver microsomes",
              "Value": 112.9,
              "Unit": "pmol/min/mg mic. protein",
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                "Source": "Publication",
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            },
            {
              "Name": "Km",
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                "Description": "Xu 2012 (corrected with microsomal fu)"
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            },
            {
              "Name": "kcat",
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                "Source": "ParameterIdentification",
                "Method": "ParameterIdentification"
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            }
          ]
        },
        {
          "InternalName": "MetabolizationLiverMicrosomes_MM",
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            {
              "Name": "In vitro Vmax for liver microsomes",
              "Value": 0.0,
              "Unit": "pmol/min/mg mic. protein"
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            {
              "Name": "Km",
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            }
          ]
        },
        {
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              "Name": "In vitro Vmax for liver microsomes",
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              "Unit": "pmol/min/mg mic. protein"
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            {
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        {
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              "Unit": "pmol/min/mg mic. protein"
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                "Method": "ParameterIdentification"
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          ]
        },
        {
          "InternalName": "MetabolizationLiverMicrosomes_MM",
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            {
              "Name": "In vitro Vmax for liver microsomes",
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              "Unit": "pmol/min/mg mic. protein"
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            {
              "Name": "Km",
              "Value": 61.62,
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          ]
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      ],
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            "Description": "Chemicalize"
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        },
        {
          "Name": "Molecular weight",
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            "Description": "Chemicalize"
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        {
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          ]
        }
      ],
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        {
          "Name": "Measurement",
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              "Name": "Fraction unbound (plasma, reference value)",
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      ],
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        {
          "Name": "Chemicalize",
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            {
              "Name": "Solubility at reference pH",
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              "Name": "Solubility gain per charge",
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            {
              "Name": "GFR fraction",
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          ]
        },
        {
          "InternalName": "MetabolizationLiverMicrosomes_MM",
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            {
              "Name": "In vitro Vmax for liver microsomes",
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                "Method": "ParameterIdentification"
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          ]
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          "Name": "Cl",
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            "Description": "Chemicalize"
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    {
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              "Name": "Lipophilicity",
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      ],
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        {
          "Name": "Measurement",
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              "Name": "Fraction unbound (plasma, reference value)",
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          "Name": "Chemicalize",
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            {
              "Name": "Solubility table",
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                    "X": 7.4,
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              "Name": "GFR fraction",
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        },
        {
          "InternalName": "MetabolizationLiverMicrosomes_MM",
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            {
              "Name": "In vitro Vmax for liver microsomes",
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            {
              "Name": "Solubility table",
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              "Name": "In vitro Vmax for liver microsomes",
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              "Name": "Solubility table",
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              "ValueOrigin": {
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              "Name": "Vmax",
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            {
              "Name": "Km",
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            {
              "Name": "kcat",
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                "Source": "Publication",
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              "Name": "Vmax",
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            },
            {
              "Name": "kcat",
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                "Source": "Publication",
                "Description": "Xia 2020"
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          ]
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              "Name": "K_kinact_half",
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        {
          "InternalName": "CompetitiveInhibition",
          "DataSource": "Jeong 2009",
          "Molecule": "CYP2B6",
          "Parameters": [
            {
              "Name": "Ki",
              "Value": 0.072738053,
              "Unit": "µmol/l",
              "ValueOrigin": {
                "Source": "ParameterIdentification",
                "Method": "ParameterIdentification"
              }
            }
          ]
        },
        {
          "InternalName": "CompetitiveInhibition",
          "DataSource": "Jeong 2009",
          "Molecule": "CYP2C19",
          "Parameters": [
            {
              "Name": "Ki",
              "Value": 4.567,
              "Unit": "µmol/l",
              "ValueOrigin": {
                "Source": "Publication",
                "Method": "InVitro",
                "Description": "Jeong 2009"
              }
            }
          ]
        }
      ],
      "CalculationMethods": [
        "Cellular partition coefficient method - Poulin and Theil",
        "Cellular permeability - PK-Sim Standard"
      ],
      "Parameters": [
        {
          "Name": "F",
          "Value": 3.0,
          "ValueOrigin": {
            "Source": "Unknown"
          }
        },
        {
          "Name": "Molecular weight",
          "Value": 349.3,
          "Unit": "g/mol"
        }
      ]
    },
    {
      "Name": "Fluvoxamine",
      "IsSmallMolecule": true,
      "Lipophilicity": [
        {
          "Name": "PI",
          "Parameters": [
            {
              "Name": "Lipophilicity",
              "Value": 3.5726507829,
              "Unit": "Log Units",
              "ValueOrigin": {
                "Source": "ParameterIdentification",
                "Method": "ParameterIdentification",
                "Description": "Final_fit"
              }
            }
          ]
        }
      ],
      "FractionUnbound": [
        {
          "Name": "Claassen, 1983",
          "Species": "Human",
          "Parameters": [
            {
              "Name": "Fraction unbound (plasma, reference value)",
              "Value": 0.23,
              "ValueOrigin": {
                "Source": "Publication",
                "Method": "Unknown",
                "Description": "Claassen et al., Review of the animal pharmacology and pharmacokinetics of fluvoxamine. Br. J. Clin. Pharmacol. 15, 349S-355S (1983)."
              }
            }
          ],
          "Description": "-"
        }
      ],
      "Solubility": [
        {
          "Name": "Water",
          "Parameters": [
            {
              "Name": "Solubility at reference pH",
              "Value": 14.66,
              "Unit": "mg/ml"
            }
          ],
          "Description": "MSDS"
        }
      ],
      "IntestinalPermeability": [
        {
          "Name": "Fitted",
          "Parameters": [
            {
              "Name": "Specific intestinal permeability (transcellular)",
              "Value": 2.7380788903E-06,
              "Unit": "dm/min",
              "ValueOrigin": {
                "Source": "ParameterIdentification",
                "Method": "ParameterIdentification",
                "Description": "Final_fit"
              }
            }
          ]
        }
      ],
      "PkaTypes": [
        {
          "Type": "Base",
          "Pka": 9.4
        }
      ],
      "Processes": [
        {
          "InternalName": "MetabolizationLiverMicrosomes_MM",
          "DataSource": "Fit",
          "Molecule": "CYP1A2",
          "Parameters": [
            {
              "Name": "Content of CYP proteins in liver microsomes",
              "Value": 45.0,
              "Unit": "pmol/mg mic. protein"
            },
            {
              "Name": "Km",
              "Value": 0.0073460807948,
              "Unit": "µmol/l",
              "ValueOrigin": {
                "Source": "ParameterIdentification",
                "Method": "ParameterIdentification",
                "Description": "Final_fit"
              }
            },
            {
              "Name": "kcat",
              "Value": 0.0155447966,
              "Unit": "1/min",
              "ValueOrigin": {
                "Source": "ParameterIdentification",
                "Method": "ParameterIdentification",
                "Description": "Final_fit"
              }
            }
          ]
        },
        {
          "InternalName": "GlomerularFiltration",
          "DataSource": "4% Urine",
          "Species": "Human"
        },
        {
          "InternalName": "rCYP450_MM",
          "DataSource": "Miura2007",
          "Molecule": "CYP2D6",
          "Parameters": [
            {
              "Name": "In vitro Vmax/recombinant enzyme",
              "Value": 0.69,
              "Unit": "pmol/min/pmol rec. enzyme"
            },
            {
              "Name": "Km",
              "Value": 76.3,
              "Unit": "µmol/l"
            },
            {
              "Name": "kcat",
              "Value": 110.5561921693,
              "Unit": "1/min",
              "ValueOrigin": {
                "Source": "ParameterIdentification",
                "Method": "ParameterIdentification",
                "Description": "Final_fit"
              }
            }
          ]
        },
        {
          "InternalName": "MixedInhibition",
          "DataSource": "Karjalainen2008/Yao2001",
          "Molecule": "CYP1A2",
          "Parameters": [
            {
              "Name": "Ki_c",
              "Value": 10.0,
              "Unit": "nmol/l",
              "ValueOrigin": {
                "Source": "Publication",
                "Method": "InVitro",
                "Description": "Karjalainen et al. In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions. Basic Clin. Pharmacol. Toxicol. 103, 157–65 (2008) and Yao, C. et al. Fluvoxamine-theophylline interaction: gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2. Clin. Pharmacol. Ther. 70, 415–24 (2001)"
              }
            },
            {
              "Name": "Ki_u",
              "Value": 10.0,
              "Unit": "nmol/l",
              "ValueOrigin": {
                "Source": "Publication",
                "Method": "InVitro",
                "Description": "Karjalainen et al. In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions. Basic Clin. Pharmacol. Toxicol. 103, 157–65 (2008) and Yao, C. et al. Fluvoxamine-theophylline interaction: gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2. Clin. Pharmacol. Ther. 70, 415–24 (2001)"
              }
            }
          ]
        },
        {
          "InternalName": "CompetitiveInhibition",
          "DataSource": "Olesen2000/Yao2001",
          "Molecule": "CYP3A4",
          "Parameters": [
            {
              "Name": "Ki",
              "Value": 1.6,
              "Unit": "µmol/l",
              "ValueOrigin": {
                "Source": "Publication",
                "Method": "InVitro",
                "Description": "Olesen et al. Fluvoxamine-Clozapine drug interaction: inhibition in vitro of five cytochrome P450 isoforms involved in clozapine metabolism. J. Clin. Psychopharmacol. 20, 35–42 (2000) and Yao, C. et al. Fluvoxamine-theophylline interaction: gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2. Clin. Pharmacol. Ther. 70, 415–24 (2001)"
              }
            }
          ]
        },
        {
          "InternalName": "CompetitiveInhibition",
          "DataSource": "Foti 2008",
          "Molecule": "CYP2C19",
          "Parameters": [
            {
              "Name": "Ki",
              "Value": 0.013,
              "Unit": "µmol/l",
              "ValueOrigin": {
                "Source": "Publication"
              }
            }
          ]
        },
        {
          "InternalName": "CompetitiveInhibition",
          "DataSource": "Hesse 2000",
          "Molecule": "CYP2B6",
          "Parameters": [
            {
              "Name": "Ki",
              "Value": 4.02,
              "Unit": "µmol/l",
              "ValueOrigin": {
                "Source": "Publication"
              }
            }
          ]
        }
      ],
      "CalculationMethods": [
        "Cellular partition coefficient method - Schmitt",
        "Cellular permeability - PK-Sim Standard"
      ],
      "Parameters": [
        {
          "Name": "Molecular weight",
          "Value": 318.335,
          "Unit": "g/mol"
        }
      ]
    }
  ],
  "Formulations": [
    {
      "Name": "Fluvoxamine - Solution",
      "FormulationType": "Formulation_Dissolved"
    },
    {
      "Name": "Voriconazole - Tablet",
      "FormulationType": "Formulation_Tablet_Weibull",
      "Parameters": [
        {
          "Name": "Dissolution time (50% dissolved)",
          "Value": 30.0,
          "Unit": "min"
        },
        {
          "Name": "Lag time",
          "Value": 0.0,
          "Unit": "min"
        },
        {
          "Name": "Dissolution shape",
          "Value": 1.29
        },
        {
          "Name": "Use as suspension",
          "Value": 1.0
        }
      ]
    },
    {
      "Name": "Bupropion - Capsule (Geneva Cocktai)",
      "FormulationType": "Formulation_Tablet_Weibull",
      "Parameters": [
        {
          "Name": "Dissolution time (50% dissolved)",
          "Value": 10.6360885426,
          "Unit": "min",
          "ValueOrigin": {
            "Source": "ParameterIdentification",
            "Method": "ParameterIdentification",
            "Description": "Value updated from 'Parameter Identification 11' on 2020-09-16 22:09"
          }
        },
        {
          "Name": "Lag time",
          "Value": 0.0,
          "Unit": "min"
        },
        {
          "Name": "Dissolution shape",
          "Value": 4.4252031231,
          "ValueOrigin": {
            "Source": "ParameterIdentification",
            "Method": "ParameterIdentification",
            "Description": "Value updated from 'Parameter Identification 11' on 2020-09-16 22:09"
          }
        },
        {
          "Name": "Use as suspension",
          "Value": 1.0
        }
      ]
    }
  ],
  "Protocols": [
    {
      "Name": "Bupropion - po, 25 mg sd",
      "DosingInterval": "Single",
      "Schemas": [
        {
          "Name": "Schema 1",
          "SchemaItems": [
            {
              "Name": "Schema Item 1",
              "ApplicationType": "Oral",
              "FormulationKey": "Formulation",
              "Parameters": [
                {
                  "Name": "Start time",
                  "Value": 12.0,
                  "Unit": "h"
                },
                {
                  "Name": "InputDose",
                  "Value": 21.7,
                  "Unit": "mg"
                },
                {
                  "Name": "Volume of water/body weight",
                  "Value": 3.5,
                  "Unit": "ml/kg"
                }
              ]
            }
          ],
          "Parameters": [
            {
              "Name": "Start time",
              "Value": 168.0,
              "Unit": "h",
              "ValueOrigin": {
                "Source": "Unknown"
              }
            }
          ]
        }
      ],
      "TimeUnit": "h"
    },
    {
      "Name": "Voriconazole - po, 400 mg sd",
      "DosingInterval": "Single",
      "Schemas": [
        {
          "Name": "Schema 1",
          "SchemaItems": [
            {
              "Name": "Schema Item 1",
              "ApplicationType": "Oral",
              "FormulationKey": "Formulation",
              "Parameters": [
                {
                  "Name": "Start time",
                  "Value": 0.0,
                  "Unit": "h"
                },
                {
                  "Name": "InputDose",
                  "Value": 400.0,
                  "Unit": "mg"
                },
                {
                  "Name": "Volume of water/body weight",
                  "Value": 3.5,
                  "Unit": "ml/kg"
                }
              ]
            }
          ],
          "Parameters": [
            {
              "Name": "Start time",
              "Value": 178.0,
              "Unit": "h",
              "ValueOrigin": {
                "Source": "Unknown"
              }
            },
            {
              "Name": "NumberOfRepetitions",
              "Value": 1.0,
              "ValueOrigin": {
                "Source": "Unknown"
              }
            },
            {
              "Name": "TimeBetweenRepetitions",
              "Value": 0.0,
              "Unit": "h",
              "ValueOrigin": {
                "Source": "Unknown"
              }
            }
          ]
        }
      ],
      "TimeUnit": "h"
    },
    {
      "Name": "Fluvoxamine - po, 50 mg md",
      "DosingInterval": "Single",
      "Schemas": [
        {
          "Name": "Schema 1",
          "SchemaItems": [
            {
              "Name": "Schema Item 1",
              "ApplicationType": "Oral",
              "FormulationKey": "Formulation",
              "Parameters": [
                {
                  "Name": "InputDose",
                  "Value": 36.64,
                  "Unit": "mg"
                }
              ]
            }
          ],
          "Parameters": [
            {
              "Name": "Start time",
              "Value": 178.0,
              "Unit": "h"
            },
            {
              "Name": "NumberOfRepetitions",
              "Value": 1.0
            },
            {
              "Name": "TimeBetweenRepetitions",
              "Value": 0.0,
              "Unit": "h"
            }
          ]
        },
        {
          "Name": "Schema 2",
          "SchemaItems": [
            {
              "Name": "Schema Item 1",
              "ApplicationType": "Oral",
              "FormulationKey": "Formulation",
              "Parameters": [
                {
                  "Name": "Start time",
                  "Value": 0.0,
                  "Unit": "h"
                },
                {
                  "Name": "InputDose",
                  "Value": 36.64,
                  "Unit": "mg"
                },
                {
                  "Name": "Volume of water/body weight",
                  "Value": 3.5,
                  "Unit": "ml/kg"
                }
              ]
            }
          ],
          "Parameters": [
            {
              "Name": "Start time",
              "Value": 168.0,
              "Unit": "h",
              "ValueOrigin": {
                "Source": "Unknown"
              }
            }
          ]
        }
      ],
      "TimeUnit": "h"
    }
  ],
  "Simulations": [
    {
      "Name": "Bosilkovska 2014 - Bupropion 25 mg Capsule + 50 mg Fluvoxamine + 400 mg Voriconazole (n=10)",
      "Model": "4Comp",
      "ObservedData": [
        "Bosilkovska 2014 DDI Inhibitor - Bupropion (n=10)",
        "Bosilkovska 2014 DDI Inhibitor - Hydroxyburpopion (n=10)"
      ],
      "Solver": {},
      "OutputSchema": [
        {
          "Parameters": [
            {
              "Name": "Start time",
              "Value": 0.0,
              "Unit": "h"
            },
            {
              "Name": "End time",
              "Value": 150.0,
              "Unit": "h",
              "ValueOrigin": {
                "Source": "Unknown"
              }
            },
            {
              "Name": "Resolution",
              "Value": 0.5,
              "Unit": "pts/h",
              "ValueOrigin": {
                "Source": "Unknown"
              }
            }
          ]
        },
        {
          "Parameters": [
            {
              "Name": "Start time",
              "Value": 150.0,
              "Unit": "h",
              "ValueOrigin": {
                "Source": "Unknown"
              }
            },
            {
              "Name": "End time",
              "Value": 270.0,
              "Unit": "h",
              "ValueOrigin": {
                "Source": "Unknown"
              }
            },
            {
              "Name": "Resolution",
              "Value": 20.0,
              "Unit": "pts/h",
              "ValueOrigin": {
                "Source": "Unknown"
              }
            }
          ]
        }
      ],
      "Parameters": [
        {
          "Path": "Applications|Bupropion - po, 25 mg sd|Bupropion - Capsule (Geneva Cocktai)|Application_1|ProtocolSchemaItem|Volume of water/body weight",
          "Value": 3.5,
          "Unit": "ml/kg"
        },
        {
          "Path": "Applications|Fluvoxamine - po, 50 mg md|Fluvoxamine - Solution|Application_1|ProtocolSchemaItem|Volume of water/body weight",
          "Value": 3.5,
          "Unit": "ml/kg"
        },
        {
          "Path": "Applications|Fluvoxamine - po, 50 mg md|Fluvoxamine - Solution|Application_2|ProtocolSchemaItem|Volume of water/body weight",
          "Value": 3.5,
          "Unit": "ml/kg"
        },
        {
          "Path": "Applications|Voriconazole - po, 400 mg sd|Voriconazole - Tablet|Application_1|ProtocolSchemaItem|Volume of water/body weight",
          "Value": 3.5,
          "Unit": "ml/kg"
        }
      ],
      "OutputSelections": [
        "Organism|PeripheralVenousBlood|Bupropion|Plasma (Peripheral Venous Blood)",
        "Organism|PeripheralVenousBlood|Hydroxybupropion|Plasma (Peripheral Venous Blood)",
        "Organism|PeripheralVenousBlood|Erythrohydrobupropion|Plasma (Peripheral Venous Blood)",
        "Organism|PeripheralVenousBlood|Threohydrobupropion|Plasma (Peripheral Venous Blood)",
        "Organism|PeripheralVenousBlood|Voriconazole|Plasma (Peripheral Venous Blood)",
        "Organism|PeripheralVenousBlood|Fluvoxamine|Plasma (Peripheral Venous Blood)"
      ],
      "Individual": "Bosilkovska 2014 (n=10)",
      "Compounds": [
        {
          "Name": "Bupropion",
          "CalculationMethods": [
            "Cellular partition coefficient method - PK-Sim Standard",
            "Cellular permeability - Charge dependent Schmitt"
          ],
          "Alternatives": [
            {
              "AlternativeName": "Fit",
              "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY"
            }
          ],
          "Processes": [
            {
              "MoleculeName": "CYP3A4"
            },
            {
              "MoleculeName": "CYP2D6"
            },
            {
              "MoleculeName": "UGT2B7"
            },
            {
              "Name": "CYP2C19-Chen 2010",
              "MoleculeName": "CYP2C19"
            },
            {
              "Name": "HSD11B1-Wang 2010 - Threohydrobupropion",
              "MoleculeName": "HSD11B1",
              "MetaboliteName": "Threohydrobupropion"
            },
            {
              "Name": "HSD11B1-Wang 2010 - Erythrohydrobupropion",
              "MoleculeName": "HSD11B1",
              "MetaboliteName": "Erythrohydrobupropion"
            },
            {
              "Name": "CYP2B6-*1 allele 1",
              "MoleculeName": "CYP2B6",
              "MetaboliteName": "Hydroxybupropion"
            },
            {
              "Name": "CYP2B6-*6 allele 2",
              "MoleculeName": "CYP2B6"
            },
            {
              "MoleculeName": "CYP1A2"
            },
            {
              "Name": "Glomerular Filtration-GFR",
              "SystemicProcessType": "GFR"
            },
            {
              "MoleculeName": "CYP3A4"
            },
            {
              "MoleculeName": "CYP2D6"
            },
            {
              "MoleculeName": "UGT2B7"
            },
            {
              "MoleculeName": "CYP2C19"
            },
            {
              "MoleculeName": "HSD11B1"
            },
            {
              "MoleculeName": "CYP2B6"
            },
            {
              "Name": "Binding Partner-Assumed",
              "MoleculeName": "Binding Partner (NRT)"
            },
            {
              "MoleculeName": "CYP1A2"
            }
          ],
          "Protocol": {
            "Name": "Bupropion - po, 25 mg sd",
            "Formulations": [
              {
                "Name": "Bupropion - Capsule (Geneva Cocktai)",
                "Key": "Formulation"
              }
            ]
          }
        },
        {
          "Name": "Hydroxybupropion",
          "CalculationMethods": [
            "Cellular partition coefficient method - Berezhkovskiy",
            "Cellular permeability - Charge dependent Schmitt"
          ],
          "Processes": [
            {
              "MoleculeName": "CYP3A4"
            },
            {
              "MoleculeName": "CYP2D6"
            },
            {
              "MoleculeName": "UGT2B7"
            },
            {
              "MoleculeName": "CYP2C19"
            },
            {
              "MoleculeName": "HSD11B1"
            },
            {
              "Name": "UGT2B7-Gufford 2016",
              "MoleculeName": "CYP2B6"
            },
            {
              "MoleculeName": "CYP1A2"
            },
            {
              "Name": "Glomerular Filtration-GFR",
              "SystemicProcessType": "GFR"
            }
          ]
        },
        {
          "Name": "Erythrohydrobupropion",
          "CalculationMethods": [
            "Cellular partition coefficient method - Berezhkovskiy",
            "Cellular permeability - Charge dependent Schmitt"
          ],
          "Processes": [
            {
              "MoleculeName": "CYP3A4"
            },
            {
              "MoleculeName": "CYP2D6"
            },
            {
              "MoleculeName": "UGT2B7"
            },
            {
              "MoleculeName": "CYP2C19"
            },
            {
              "MoleculeName": "HSD11B1"
            },
            {
              "Name": "UGT2B7-Gufford 2016",
              "MoleculeName": "CYP2B6"
            },
            {
              "MoleculeName": "CYP1A2"
            },
            {
              "Name": "Glomerular Filtration-GFR",
              "SystemicProcessType": "GFR"
            }
          ]
        },
        {
          "Name": "Threohydrobupropion",
          "CalculationMethods": [
            "Cellular partition coefficient method - Berezhkovskiy",
            "Cellular permeability - Charge dependent Schmitt"
          ],
          "Processes": [
            {
              "MoleculeName": "CYP3A4"
            },
            {
              "MoleculeName": "CYP2D6"
            },
            {
              "MoleculeName": "UGT2B7"
            },
            {
              "MoleculeName": "CYP2C19"
            },
            {
              "MoleculeName": "HSD11B1"
            },
            {
              "Name": "UGT2B7-Gufford 2016",
              "MoleculeName": "CYP2B6"
            },
            {
              "MoleculeName": "CYP1A2"
            },
            {
              "Name": "Glomerular Filtration-GFR",
              "SystemicProcessType": "GFR"
            }
          ]
        },
        {
          "Name": "Voriconazole",
          "CalculationMethods": [
            "Cellular partition coefficient method - Poulin and Theil",
            "Cellular permeability - PK-Sim Standard"
          ],
          "Alternatives": [
            {
              "AlternativeName": "Optimized",
              "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY"
            }
          ],
          "Processes": [
            {
              "Name": "CYP3A4-Xia 2020 - CYP3A4",
              "MoleculeName": "CYP3A4"
            },
            {
              "MoleculeName": "CYP2D6"
            },
            {
              "MoleculeName": "UGT2B7"
            },
            {
              "Name": "CYP2C19-Xia 2020 - CYP2C19",
              "MoleculeName": "CYP2C19"
            },
            {
              "MoleculeName": "HSD11B1"
            },
            {
              "MoleculeName": "CYP2B6"
            },
            {
              "MoleculeName": "CYP1A2"
            },
            {
              "Name": "Glomerular Filtration-GFR",
              "SystemicProcessType": "GFR"
            }
          ],
          "Protocol": {
            "Name": "Voriconazole - po, 400 mg sd",
            "Formulations": [
              {
                "Name": "Voriconazole - Tablet",
                "Key": "Formulation"
              }
            ]
          }
        },
        {
          "Name": "Fluvoxamine",
          "CalculationMethods": [
            "Cellular partition coefficient method - Schmitt",
            "Cellular permeability - PK-Sim Standard"
          ],
          "Alternatives": [
            {
              "AlternativeName": "Fitted",
              "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY"
            }
          ],
          "Processes": [
            {
              "MoleculeName": "CYP3A4"
            },
            {
              "Name": "CYP2D6-Miura2007",
              "MoleculeName": "CYP2D6"
            },
            {
              "MoleculeName": "UGT2B7"
            },
            {
              "MoleculeName": "CYP2C19"
            },
            {
              "MoleculeName": "HSD11B1"
            },
            {
              "MoleculeName": "CYP2B6"
            },
            {
              "Name": "CYP1A2-Fit",
              "MoleculeName": "CYP1A2"
            },
            {
              "Name": "Glomerular Filtration-4% Urine",
              "SystemicProcessType": "GFR"
            }
          ],
          "Protocol": {
            "Name": "Fluvoxamine - po, 50 mg md",
            "Formulations": [
              {
                "Name": "Fluvoxamine - Solution",
                "Key": "Formulation"
              }
            ]
          }
        }
      ],
      "HasResults": true,
      "IndividualAnalyses": [
        {
          "Axes": [
            {
              "Unit": "h",
              "Dimension": "Time",
              "Type": "X",
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          "Value": "Peripheral Venous Blood"
        },
        {
          "Name": "Compartment",
          "Value": "Plasma"
        }
      ],
      "Columns": [
        {
          "Name": "Conc ",
          "RelatedColumns": [
            {
              "Name": "SD ",
              "QuantityInfo": {
                "Name": "SD ",
                "Path": "Bosilkovska 2014 Control - Hydroxyburpopion (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Hydroxybupropion|SD "
              },
              "DataInfo": {
                "Origin": "ObservationAuxiliary",
                "AuxiliaryType": "ArithmeticStdDev",
                "Date": "2020-08-27T15:13:13.6425787+02:00",
                "Source": "Bosilkovska 2014 Control T=180 -.Hydroxyburpopion (PVB).SD [ng/ml]",
                "MolWeight": 255.74
              },
              "Values": [
                7.28855038,
                6.525631,
                8.898719,
                11.1016951,
                10.3389826,
                9.745349,
                7.79702425
              ],
              "Dimension": "Concentration (mass)",
              "Unit": "ng/ml"
            }
          ],
          "QuantityInfo": {
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            "Path": "Bosilkovska 2014 Control - Hydroxyburpopion (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Hydroxybupropion|Conc "
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          "DataInfo": {
            "Origin": "Observation",
            "AuxiliaryType": "Undefined",
            "Date": "2020-08-27T15:13:13.6425787+02:00",
            "Source": "Bosilkovska 2014 Control T=180 -.Hydroxyburpopion (PVB).Conc [ng/ml]",
            "MolWeight": 255.74
          },
          "Values": [
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            27.94476,
            38.1778641,
            38.32622,
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          "Unit": "ng/ml"
        }
      ],
      "BaseGrid": {
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        "QuantityInfo": {
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          "Type": "Time"
        },
        "DataInfo": {
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          "AuxiliaryType": "Undefined",
          "Date": "2020-08-27T15:13:13.6425787+02:00",
          "Source": "Bosilkovska 2014 Control T=180 -.Hydroxyburpopion (PVB).Time [h]"
        },
        "Values": [
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        "Dimension": "Time",
        "Unit": "h"
      }
    }
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  "ObservedDataClassifications": [
    {
      "Name": "Bosilkovska 2014",
      "Classifications": [
        {
          "Name": "Control",
          "Classifiables": [
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  "SimulationClassifications": [
    {
      "Name": "DDI",
      "Classifiables": [
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        "Bosilkovska 2014 - Bupropion 25 mg Capsule + 50 mg Fluvoxamine + 400 mg Voriconazole (n=10)"
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    }
  ]
}