modelL04AK01
Extends from Pharmacokinetic.Models.PK_2C_enteral.
Information
| name: | Leflunomide | |
| ATC code: | L04AK01 | route: | oral |
| compartments: | 2 | |
| dosage: | 100 | mg |
| volume of distribution: | 9.7 | L |
| clearance: | 0.047 | L/h/kg |
| other parameters in model implementation | ||
Leflunomide is an immunomodulatory agent classified as a disease-modifying antirheumatic drug (DMARD). It works primarily by inhibiting dihydroorotate dehydrogenase, thus blocking pyrimidine synthesis, and is used in the treatment of rheumatoid arthritis and psoriatic arthritis. It is approved and widely used today for these indications.
Pharmacokinetics
Pharmacokinetic parameters of leflunomide (its active metabolite A77 1726) in healthy adult volunteers after oral administration.
References
Shin, Y, et al., & Park, K (2023). Development of a population pharmacokinetic model and optimal dosing regimen of leflunomide in Korean population. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 184 106402–None. DOI:10.1016/j.ejps.2023.106402 PUBMED:https://pubmed.ncbi.nlm.nih.gov/36754259
Shi, J, et al., & Bhargava, VO (2005). Population pharmacokinetics of the active metabolite of leflunomide in pediatric subjects with polyarticular course juvenile rheumatoid arthritis. Journal of pharmacokinetics and pharmacodynamics 32(3-4) 419–439. DOI:10.1007/s10928-005-0049-8 PUBMED:https://pubmed.ncbi.nlm.nih.gov/16284916
Bohanec Grabar, P, et al., & Dolzan, V (2009). Investigation of the influence of CYP1A2 and CYP2C19 genetic polymorphism on 2-Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide (A77 1726) pharmacokinetics in leflunomide-treated patients with rheumatoid arthritis. Drug metabolism and disposition: the biological fate of chemicals 37(10) 2061–2068. DOI:10.1124/dmd.109.027482 PUBMED:https://pubmed.ncbi.nlm.nih.gov/19581389
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)