modelRegorafenib
Extends from Pharmacolibrary.Drugs.ATC.L.L01EX05.
Information
| name: | Regorafenib | |
| ATC code: | L01EX05 | route: | oral |
| compartments: | 2 | |
| dosage: | 160 | mg |
| volume of distribution: | 110 | L |
| clearance: | 3.0 | L/hr |
| other parameters in model implementation | ||
Regorafenib is an orally active multi-kinase inhibitor that targets several protein kinases involved in tumor angiogenesis, oncogenesis, and the tumor microenvironment. It is approved for the treatment of metastatic colorectal cancer, advanced gastrointestinal stromal tumors (GIST), and hepatocellular carcinoma in patients who have been previously treated with other therapies.
Pharmacokinetics
Pharmacokinetic parameters were reported in adult patients with advanced solid tumors in clinical studies, both male and female, typical population includes patients aged 40-70 years. The parameters are based on oral dosing.
References
Fukudo, M, et al., & Ueno, N (2021). Pharmacokinetics of the oral multikinase inhibitor regorafenib and its association with real-world treatment outcomes. Investigational new drugs 39(5) 1422–1431. DOI:10.1007/s10637-021-01115-4 PUBMED:https://pubmed.ncbi.nlm.nih.gov/33830408
Keunecke, A, et al., & Ploeger, BA (2020). Population pharmacokinetics of regorafenib in solid tumours: Exposure in clinical practice considering enterohepatic circulation and food intake. British journal of clinical pharmacology 86(12) 2362–2376. DOI:10.1111/bcp.14334 PUBMED:https://pubmed.ncbi.nlm.nih.gov/32358822
Fu, Q, et al., & Baker, SD (2019). Interaction Between Sex and Organic Anion-Transporting Polypeptide 1b2 on the Pharmacokinetics of Regorafenib and Its Metabolites Regorafenib-N-Oxide and Regorafenib-Glucuronide in Mice. Clinical and translational science 12(4) 400–407. DOI:10.1111/cts.12630 PUBMED:https://pubmed.ncbi.nlm.nih.gov/30955241
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)