modelJ04AM06
Extends from Pharmacokinetic.Models.PK_1C_enteral.
Information
| name: | RifampicinPyrazinamideEthambutolAndIsoniazid | |
| ATC code: | J04AM06 | route: | oral |
| compartments: | 1 | |
| dosage: | 600 | mg |
| volume of distribution: | 52 | L |
| clearance: | 8.7 | L/h |
| other parameters in model implementation | ||
This combination drug is used for the treatment of active tuberculosis infection and is composed of rifampicin, pyrazinamide, ethambutol, and isoniazid. It is an essential, approved regimen in first-line tuberculosis therapy recommended by the WHO and many national tuberculosis programs. It targets Mycobacterium tuberculosis through multiple mechanisms: rifampicin inhibits RNA synthesis, isoniazid inhibits mycolic acid synthesis, pyrazinamide disrupts membrane energetics, and ethambutol interferes with cell wall synthesis.
Pharmacokinetics
Population pharmacokinetics in adult patients with pulmonary tuberculosis receiving fixed-dose combination tablets under directly observed therapy; mixed male and female, mean age around 38 years.
References
Chen, C, et al., & Simonsson, US (2016). Population pharmacokinetics, optimised design and sample size determination for rifampicin, isoniazid, ethambutol and pyrazinamide in the mouse. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 93 319–333. DOI:10.1016/j.ejps.2016.07.017 PUBMED:https://pubmed.ncbi.nlm.nih.gov/27473307
Denti, P, et al., & Andersen, AB (2015). Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Newly Diagnosed Pulmonary TB Patients in Tanzania. PloS one 10(10) e0141002–None. DOI:10.1371/journal.pone.0141002 PUBMED:https://pubmed.ncbi.nlm.nih.gov/26501782
Langdon, G, et al., & Simonsson, US (2005). Population pharmacokinetics of rifapentine and its primary desacetyl metabolite in South African tuberculosis patients. Antimicrobial agents and chemotherapy 49(11) 4429–4436. DOI:10.1128/AAC.49.11.4429-4436.2005 PUBMED:https://pubmed.ncbi.nlm.nih.gov/16251279
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.TransferRate | ka (from PK_1C_enteral) | 0.016666666666666666 | first order absorption rate |
| Modelica.Units.SI.Time | Tlag (from PK_1C_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) |
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 |
Revisions
- 06/2025 Tomas Kulhanek, generated model from data extracted from PUBMED, DrugBank and LLM(GPT4.1)