modelC04AX33
Extends from Pharmacokinetic.Models.PK_2C.
Information
| name: | Clazosentan | |
| ATC code: | C04AX33 | route: | intravenous |
| compartments: | 2 | |
| dosage: | 15 | mg |
| volume of distribution: | 40 | L |
| clearance: | 36 | L/h |
| other parameters in model implementation | ||
Clazosentan is a selective endothelin A (ETA) receptor antagonist developed primarily for the prevention and treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH). It acts to inhibit vasoconstriction mediated by endothelin-1, thereby improving cerebral blood flow. Clazosentan is approved for use in some regions such as Japan, but not widely approved globally.
Pharmacokinetics
Pharmacokinetic parameters derived from healthy adult subjects after intravenous dosing.
References
van Giersbergen, PL, et al., & Dingemanse, J (2007). Influence of ethnic origin and sex on the pharmacokinetics of clazosentan. Journal of clinical pharmacology 47(11) 1374–1380. DOI:10.1177/0091270007307337 PUBMED:https://pubmed.ncbi.nlm.nih.gov/17906281
Henrich, A, et al., & Krause, A (2021). PK/PD modeling of a clazosentan thorough QT study with hysteresis in concentration-QT and RR-QT. Journal of pharmacokinetics and pharmacodynamics 48(2) 213–224. DOI:10.1007/s10928-020-09728-7 PUBMED:https://pubmed.ncbi.nlm.nih.gov/33389549
Volz, AK, et al., & Lehr, T (2019). Target-Mediated Population Pharmacokinetic Modeling of Endothelin Receptor Antagonists. Pharmaceutical research 37(1) 2–None. DOI:10.1007/s11095-019-2723-3 PUBMED:https://pubmed.ncbi.nlm.nih.gov/31823033
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)