modelLapatinib
Extends from Pharmacolibrary.Drugs.ATC.L.L01EH01.
Information
| name: | Lapatinib | |
| ATC code: | L01EH01 | route: | oral |
| compartments: | 2 | |
| dosage: | 1250 | mg |
| volume of distribution: | 1670 | L |
| clearance: | 4.34 | L/h |
| other parameters in model implementation | ||
Lapatinib is an oral tyrosine kinase inhibitor targeting both epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2). It is primarily used in the treatment of HER2-positive breast cancer, especially in combination with other chemotherapeutics. Lapatinib is approved for use in several countries, including the United States and the EU.
Pharmacokinetics
Pharmacokinetic parameters reported in adult female patients with advanced or metastatic HER2-positive breast cancer, following repeated oral administration.
References
Pai, SM, et al., & Berg, JK (2019). Pharmacokinetics of Lapatinib, a Nonrenally Cleared Drug, in Patients With End-Stage Renal Disease on Maintenance Hemodialysis. Journal of clinical pharmacology 59(10) 1379–1383. DOI:10.1002/jcph.1430 PUBMED:https://pubmed.ncbi.nlm.nih.gov/31074516
Nakagawa, K, et al., & Fukuoka, M (2009). Phase I dose-escalation and pharmacokinetic trial of lapatinib (GW572016), a selective oral dual inhibitor of ErbB-1 and -2 tyrosine kinases, in Japanese patients with solid tumors. Japanese journal of clinical oncology 39(2) 116–123. DOI:10.1093/jjco/hyn135 PUBMED:https://pubmed.ncbi.nlm.nih.gov/19052038
Guerin, M, et al., & Gonçalves, A (2017). PIKHER2: A phase IB study evaluating buparlisib in combination with lapatinib in trastuzumab-resistant HER2-positive advanced breast cancer. European journal of cancer (Oxford, England : 1990) 86 28–36. DOI:10.1016/j.ejca.2017.08.025 PUBMED:https://pubmed.ncbi.nlm.nih.gov/28950146
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)