modelUmbralisib

Diagram of Umbralisib

Extends from Pharmacolibrary.Drugs.ATC.L.L01EX25.

Information

name:Umbralisib
ATC code:L01EX25
route:oral
compartments:2
dosage:800mg
volume of distribution:116L
clearance:72.9L/h
other parameters in model implementation

Umbralisib is an oral, selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor with additional inhibition of casein kinase 1 epsilon (CK1ε). It is used for the treatment of certain B-cell malignancies, including marginal zone lymphoma and follicular lymphoma. It was approved by the FDA but was voluntarily withdrawn from the market in 2022 due to safety concerns.

Pharmacokinetics

Pharmacokinetic parameters as observed in adult cancer patients receiving oral umbralisib as a single agent.

References

  1. Burris, HA, et al., & O'Connor, OA (2018). Umbralisib, a novel PI3Kδ and casein kinase-1ε inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, phase 1, dose-escalation, first-in-human study. The Lancet. Oncology 19(4) 486–496. DOI:10.1016/S1470-2045(18)30082-2 PUBMED:https://pubmed.ncbi.nlm.nih.gov/29475723

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)