modelL01XJ01
Extends from Pharmacokinetic.Models.PK_1C_enteral.
Information
| name: | Vismodegib | |
| ATC code: | L01XJ01 | route: | oral |
| compartments: | 1 | |
| dosage: | 150 | mg |
| volume of distribution: | 16.4 | L |
| clearance: | 0.563 | L/h |
| other parameters in model implementation | ||
Vismodegib is an orally administered small molecule inhibitor of the Hedgehog signaling pathway, specifically targeting the smoothened (SMO) receptor. It is approved for the treatment of adults with metastatic or locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery or radiation.
Pharmacokinetics
Pharmacokinetic parameters as characterized in adult patients with advanced solid tumors, including locally advanced or metastatic basal cell carcinoma, after oral administration.
References
Abou-Alfa, GK, et al., & Graham, RA (2017). Pharmacokinetics and safety of vismodegib in patients with advanced solid malignancies and hepatic impairment. Cancer chemotherapy and pharmacology 80(1) 29–36. DOI:10.1007/s00280-017-3315-8 PUBMED:https://pubmed.ncbi.nlm.nih.gov/28523596
Frampton, JE, & Basset-Séguin, N (2018). Vismodegib: A Review in Advanced Basal Cell Carcinoma. Drugs 78(11) 1145–1156. DOI:10.1007/s40265-018-0948-9 PUBMED:https://pubmed.ncbi.nlm.nih.gov/30030732
Wong, H, et al., & Gould, SE (2011). Pharmacokinetic-pharmacodynamic analysis of vismodegib in preclinical models of mutational and ligand-dependent Hedgehog pathway activation. Clinical cancer research : an official journal of the American Association for Cancer Research 17(14) 4682–4692. DOI:10.1158/1078-0432.CCR-11-0975 PUBMED:https://pubmed.ncbi.nlm.nih.gov/21610148
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.TransferRate | ka (from PK_1C_enteral) | 0.016666666666666666 | first order absorption rate |
| Modelica.Units.SI.Time | Tlag (from PK_1C_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) |
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 |
Revisions
- 06/2025 Tomas Kulhanek, generated model from data extracted from PUBMED, DrugBank and LLM(GPT4.1)