modelTrametinib
Extends from Pharmacolibrary.Drugs.ATC.L.L01EE01.
Information
| name: | Trametinib | |
| ATC code: | L01EE01 | route: | oral |
| compartments: | 2 | |
| dosage: | 2 | mg |
| volume of distribution: | 1830 | L |
| clearance: | 3.21 | L/h |
| other parameters in model implementation | ||
Trametinib is an oral, selective MEK1 and MEK2 inhibitor used primarily in the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations. It is approved for use, often in combination with dabrafenib, and is indicated for adult patients. It helps to inhibit the mitogen-activated protein kinase (MAPK) pathway, thereby reducing tumor cell proliferation.
Pharmacokinetics
Pharmacokinetic parameters in adult patients with solid tumors and metastatic melanoma administered trametinib orally.
References
Ravix, A, et al., & Guidi, M (2024). Population Pharmacokinetics of Trametinib and Impact of Nonadherence on Drug Exposure in Oncology Patients as Part of the Optimizing Oral Targeted Anticancer Therapies Study. Cancers 16(12) –. DOI:10.3390/cancers16122193 PUBMED:https://pubmed.ncbi.nlm.nih.gov/38927898
Ouellet, D, et al., & Patel, K (2016). Population pharmacokinetics and exposure-response of trametinib, a MEK inhibitor, in patients with BRAF V600 mutation-positive melanoma. Cancer chemotherapy and pharmacology 77(4) 807–817. DOI:10.1007/s00280-016-2993-y PUBMED:https://pubmed.ncbi.nlm.nih.gov/26940938
Cox, DS, et al., & Orford, K (2015). Relative bioavailability of pediatric oral solution and tablet formulations of trametinib in adult patients with solid tumors. Clinical pharmacology in drug development 4(4) 287–294. DOI:10.1002/cpdd.152 PUBMED:https://pubmed.ncbi.nlm.nih.gov/27136909
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)