modelR07AX32

Extends from Pharmacokinetic.Models.PK_2C_enteral.

Information

name:IvacaftorTezacaftorAndElexacaftor
ATC code:R07AX32
route:oral
compartments:2
dosage:200mg
volume of distribution:130L
clearance:17.3L/h
other parameters in model implementation

Ivacaftor, tezacaftor, and elexacaftor are a fixed-dose triple combination therapy used in the treatment of cystic fibrosis in patients with specific mutations in the CFTR gene. This combination increases the quantity and function of the CFTR protein at the cell surface. The drug combination is FDA and EMA approved for use in eligible patients with cystic fibrosis.

Pharmacokinetics

Pharmacokinetic parameters reported in healthy adult subjects and cystic fibrosis patients (mixed population, both sexes, age 12 and above), after repeated oral dosing at recommended therapeutic doses.

References

    Parameters

    TypeNameDefaultDescription
    Modelica.Units.SI.Massweight (from PK_1C)75patient weight (kg)
    Modelica.Units.SI.SpecificVolumeVdPerKg (from PK_1C)0.9Volume of distribution (L/kg)
    Modelica.Units.SI.MassFractionF (from PK_1C)0.8bioavailiability (0-1)
    Pharmacolibrary.Types.ClearanceCl (from PK_1C)20clearance
    Modelica.Units.SI.TimeadminTime (from PK_1C)60first administration time (s)
    Modelica.Units.SI.TimeadminDuration (from PK_1C)600administration duration (s)
    Modelica.Units.SI.TimeadminPeriod (from PK_1C)8*60*60period of administration (default 8 hours)(s)
    Pharmacolibrary.Types.MassadminMass (from PK_1C)1000administration mass (mg)
    IntegeradminCount (from PK_1C)8number of dose administered (1)
    Pharmacolibrary.Types.VolumeVd (from PK_1C)VdPerKg*weightVolume of distribution (m3)
    Pharmacolibrary.Types.MassConcentrationCmin (from PK_1C)0.004minimal therapeutic range
    Pharmacolibrary.Types.MassConcentrationCmax (from PK_1C)0.008minimal therapeutic range
    Pharmacolibrary.Types.MassConcentrationCtox_peak (from PK_1C)0.012toxicity peak level
    Pharmacolibrary.Types.MassConcentrationCtox_trough (from PK_1C)0.006toxicity trough level
    Pharmacolibrary.Types.VolumeVdp (from PK_2C)VdpPerKg*weightVolume of distribution (m3)
    Modelica.Units.SI.SpecificVolumeVdpPerKg (from PK_2C)0.9Volume of distribution peripheral(l/kg)
    Pharmacolibrary.Types.Clearancek12 (from PK_2C)1intercompartmental C-P clearance
    Pharmacolibrary.Types.Clearancek21 (from PK_2C)1intercompartmental P-C clearance
    Pharmacolibrary.Types.TransferRateka (from PK_2C_enteral)0.016666666666666666first order absorption rate
    Modelica.Units.SI.TimeTlag (from PK_2C_enteral)600delay between oral administration and absorption (default 10min)

    Connectors

    TypeNameDefaultDescription
    Types.ConcentrationOutputC_central (from PK_1C)
    Interfaces.ConcentrationPort_bcentralCPort (from PK_1C)
    Interfaces.ConcentrationPort_bperipheralCPort (from PK_2C)
    Pharmacolibrary.Types.ConcentrationOutputC_peripheral1 (from PK_2C)

    Components

    TypeNameDefaultDescription
    Pharmacokinetic.NoPerfusedTissueCompartmentcentral (from PK_1C)
    Pharmacokinetic.ClearanceDrivenEliminationelim (from PK_1C)
    Sources.PeriodicDoseperiodicDose (from PK_1C)
    Modelica.Units.SI.Timet1_2 (from PK_1C)elimination half-life
    Pharmacolibrary.Pharmacokinetic.TransferFirstOrderNonSymtransfer (from PK_2C)
    Pharmacolibrary.Pharmacokinetic.NoPerfusedTissueCompartmentperipheral (from PK_2C)

    Revisions

    • 06/2025 Tomas Kulhanek, generated model from data extracted from PUBMED, DrugBank and LLM(GPT4.1)