modelL01XJ03
Extends from Pharmacokinetic.Models.PK_2C_enteral.
Information
| name: | Glasdegib | |
| ATC code: | L01XJ03 | route: | oral |
| compartments: | 2 | |
| dosage: | 100 | mg |
| volume of distribution: | 376 | L |
| clearance: | 16.2 | L/h |
| other parameters in model implementation | ||
Glasdegib is an oral small-molecule inhibitor of the hedgehog (Hh) signaling pathway, specifically targeting Smoothened (SMO). It is primarily used in combination with low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adult patients who are 75 years or older or who have comorbidities that preclude the use of intensive chemotherapy. Glasdegib is FDA-approved.
Pharmacokinetics
Pharmacokinetic parameters reported for adult patients with cancer (including AML), both male and female, after oral administration of glasdegib. Parameters represent a typical administration in clinical settings.
References
Lin, S, et al., & Ruiz-Garcia, A (2020). Population Pharmacokinetics of Glasdegib in Patients With Advanced Hematologic Malignancies and Solid Tumors. Journal of clinical pharmacology 60(5) 605–616. DOI:10.1002/jcph.1556 PUBMED:https://pubmed.ncbi.nlm.nih.gov/31769065
Gerds, AT, et al., & Talpaz, M (2019). Phase 1/2 trial of glasdegib in patients with primary or secondary myelofibrosis previously treated with ruxolitinib. Leukemia research 79 38–44. DOI:10.1016/j.leukres.2019.02.012 PUBMED:https://pubmed.ncbi.nlm.nih.gov/30849661
Lin, S, et al., & Ruiz-Garcia, A (2020). An evaluation of overall survival in patients with newly diagnosed acute myeloid leukemia and the relationship with glasdegib treatment and exposure. Cancer chemotherapy and pharmacology 86(4) 451–459. DOI:10.1007/s00280-020-04132-x PUBMED:https://pubmed.ncbi.nlm.nih.gov/32885274
Parameters
| Type | Name | Default | Description |
|---|---|---|---|
| Modelica.Units.SI.Mass | weight (from PK_1C) | 75 | patient weight (kg) |
| Modelica.Units.SI.SpecificVolume | VdPerKg (from PK_1C) | 0.9 | Volume of distribution (L/kg) |
| Modelica.Units.SI.MassFraction | F (from PK_1C) | 0.8 | bioavailiability (0-1) |
| Pharmacolibrary.Types.Clearance | Cl (from PK_1C) | 20 | clearance |
| Modelica.Units.SI.Time | adminTime (from PK_1C) | 60 | first administration time (s) |
| Modelica.Units.SI.Time | adminDuration (from PK_1C) | 600 | administration duration (s) |
| Modelica.Units.SI.Time | adminPeriod (from PK_1C) | 8*60*60 | period of administration (default 8 hours)(s) |
| Pharmacolibrary.Types.Mass | adminMass (from PK_1C) | 1000 | administration mass (mg) |
| Integer | adminCount (from PK_1C) | 8 | number of dose administered (1) |
| Pharmacolibrary.Types.Volume | Vd (from PK_1C) | VdPerKg*weight | Volume of distribution (m3) |
| Pharmacolibrary.Types.MassConcentration | Cmin (from PK_1C) | 0.004 | minimal therapeutic range |
| Pharmacolibrary.Types.MassConcentration | Cmax (from PK_1C) | 0.008 | minimal therapeutic range |
| Pharmacolibrary.Types.MassConcentration | Ctox_peak (from PK_1C) | 0.012 | toxicity peak level |
| Pharmacolibrary.Types.MassConcentration | Ctox_trough (from PK_1C) | 0.006 | toxicity trough level |
| Pharmacolibrary.Types.Volume | Vdp (from PK_2C) | VdpPerKg*weight | Volume of distribution (m3) |
| Modelica.Units.SI.SpecificVolume | VdpPerKg (from PK_2C) | 0.9 | Volume of distribution peripheral(l/kg) |
| Pharmacolibrary.Types.Clearance | k12 (from PK_2C) | 1 | intercompartmental C-P clearance |
| Pharmacolibrary.Types.Clearance | k21 (from PK_2C) | 1 | intercompartmental P-C clearance |
| Pharmacolibrary.Types.TransferRate | ka (from PK_2C_enteral) | 0.016666666666666666 | first order absorption rate |
| Modelica.Units.SI.Time | Tlag (from PK_2C_enteral) | 600 | delay between oral administration and absorption (default 10min) |
Connectors
| Type | Name | Default | Description |
|---|---|---|---|
| Types.ConcentrationOutput | C_central (from PK_1C) | ||
| Interfaces.ConcentrationPort_b | centralCPort (from PK_1C) | ||
| Interfaces.ConcentrationPort_b | peripheralCPort (from PK_2C) | ||
| Pharmacolibrary.Types.ConcentrationOutput | C_peripheral1 (from PK_2C) |
Components
| Type | Name | Default | Description |
|---|---|---|---|
| Pharmacokinetic.NoPerfusedTissueCompartment | central (from PK_1C) | ||
| Pharmacokinetic.ClearanceDrivenElimination | elim (from PK_1C) | ||
| Sources.PeriodicDose | periodicDose (from PK_1C) | ||
| Modelica.Units.SI.Time | t1_2 (from PK_1C) | elimination half-life | |
| Pharmacolibrary.Pharmacokinetic.TransferFirstOrderNonSym | transfer (from PK_2C) | ||
| Pharmacolibrary.Pharmacokinetic.NoPerfusedTissueCompartment | peripheral (from PK_2C) |
Revisions
- 06/2025 Tomas Kulhanek, generated model from data extracted from PUBMED, DrugBank and LLM(GPT4.1)