modelL04AX03
Extends from Pharmacokinetic.Models.PK_2C.
Information
| name: | Methotrexate | |
| ATC code: | L04AX03 | route: | intravenous |
| compartments: | 2 | |
| dosage: | 1000 | mg |
| volume of distribution: | 21.13 | L |
| clearance: | 6.19 | L/h |
| other parameters in model implementation | ||
Methotrexate is an antimetabolite and antifolate drug, widely used in the treatment of various cancers (e.g., leukemia, lymphoma, breast cancer) and autoimmune diseases such as rheumatoid arthritis and psoriasis. It inhibits dihydrofolate reductase, blocking DNA synthesis and cell replication. Methotrexate is approved and used in clinical practice today for both oncological and non-oncological indications.
Pharmacokinetics
Pharmacokinetic parameters reported in adults, primarily cancer patients, after intravenous administration. Data based on population PK studies. Parameters represent typical values in adult patients with normal renal function.
References
Nader, A, et al., & Wilby, KJ (2017). Population Pharmacokinetics of Intravenous Methotrexate in Patients with Hematological Malignancies: Utilization of Routine Clinical Monitoring Parameters. European journal of drug metabolism and pharmacokinetics 42(2) 221–228. DOI:10.1007/s13318-016-0338-1 PUBMED:https://pubmed.ncbi.nlm.nih.gov/27059845
Medellin-Garibay, SE, et al., & Romano-Moreno, S (2020). Population pharmacokinetics of methotrexate in Mexican pediatric patients with acute lymphoblastic leukemia. Cancer chemotherapy and pharmacology 85(1) 21–31. DOI:10.1007/s00280-019-03977-1 PUBMED:https://pubmed.ncbi.nlm.nih.gov/31673826
Shi, ZY, et al., & Yan, D (2020). Population pharmacokinetics of high-dose methotrexate in Chinese pediatric patients with medulloblastoma. Biopharmaceutics & drug disposition 41(3) 101–110. DOI:10.1002/bdd.2221 PUBMED:https://pubmed.ncbi.nlm.nih.gov/32017134
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 |
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)