modelLarotrectinib

Diagram of Larotrectinib

Extends from Pharmacolibrary.Drugs.ATC.L.L01EX12.

Information

name:Larotrectinib
ATC code:L01EX12
route:oral
compartments:2
dosage:100mg
volume of distribution:48.3L
clearance:17.4L/h
other parameters in model implementation

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with solid tumors harboring an NTRK gene fusion. It is indicated for use irrespective of tumor type or site of origin, provided the tumor carries an NTRK gene fusion. Larotrectinib is approved for use in the US, EU, and other territories.

Pharmacokinetics

Population pharmacokinetics in adult and pediatric patients with NTRK fusion-positive tumors; parameters are derived from a two-compartment model with first-order absorption following oral administration of varied doses (including 100 mg twice daily in adults).

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)