modelFexinidazole
Extends from Pharmacolibrary.Drugs.ATC.P.P01CA03.
Information
| name: | Fexinidazole | |
| ATC code: | P01CA03 | route: | oral |
| compartments: | 2 | |
| dosage: | 1800 | mg |
| volume of distribution: | 312 | L |
| clearance: | 12.5 | L/h |
| other parameters in model implementation | ||
Fexinidazole is an oral nitroimidazole-based medication indicated for the treatment of human African trypanosomiasis (sleeping sickness), caused by Trypanosoma brucei gambiense. It is the first all-oral regimen for this disease and was approved by the European Medicines Agency and WHO for this indication. It is used in both first and second stage disease.
Pharmacokinetics
Pharmacokinetic parameters following oral administration of fexinidazole in adult patients with sleeping sickness. Parameters are based on PopPK modeling in infected individuals (adults) from a phase II/III clinical study.
References
Burrell-Saward, H, et al., & Croft, SL (2017). Dose-dependent effect and pharmacokinetics of fexinidazole and its metabolites in a mouse model of human African trypanosomiasis. International journal of antimicrobial agents 50(2) 203–209. DOI:10.1016/j.ijantimicag.2017.01.038 PUBMED:https://pubmed.ncbi.nlm.nih.gov/28552771
Tarral, A, et al., & Strub-Wourgaft, N (2014). Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: first-in-human studies. Clinical pharmacokinetics 53(6) 565–580. DOI:10.1007/s40262-014-0136-3 PUBMED:https://pubmed.ncbi.nlm.nih.gov/24535888
Watson, JA, et al., & White, NJ (2019). Pharmacokinetic-Pharmacodynamic Assessment of the Hepatic and Bone Marrow Toxicities of the New Trypanoside Fexinidazole. Antimicrobial agents and chemotherapy 63(4) –. DOI:10.1128/AAC.02515-18 PUBMED:https://pubmed.ncbi.nlm.nih.gov/30670439
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)