modelNirmatrelvirAndRitonavir
Extends from Pharmacolibrary.Drugs.ATC.J.J05AE30.
Information
| name: | NirmatrelvirAndRitonavir | |
| ATC code: | J05AE30 | route: | oral |
| compartments: | 1 | |
| dosage: | 300 | mg |
| volume of distribution: | 105.5 | L |
| clearance: | 8.99 | L/h |
| other parameters in model implementation | ||
Nirmatrelvir and ritonavir is a combination antiviral therapy used primarily in the treatment of COVID-19. Nirmatrelvir is a SARS-CoV-2 3CL protease inhibitor, while ritonavir acts as a pharmacokinetic enhancer by inhibiting CYP3A-mediated metabolism, thereby increasing plasma concentrations of nirmatrelvir. This combination (marketed as Paxlovid) is approved for emergency use and treatment of COVID-19 in many countries.
Pharmacokinetics
Representative pharmacokinetic parameters for nirmatrelvir/ritonavir in healthy adult subjects after oral administration.
References
Hammond, J, et al., & Rusnak, JM (2022). Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. The New England journal of medicine 386(15) 1397–1408. DOI:10.1056/NEJMoa2118542 PUBMED:https://pubmed.ncbi.nlm.nih.gov/35172054
Gerhart, J, et al., & Damle, B (2024). A Comprehensive Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Nirmatrelvir/Ritonavir. Clinical pharmacokinetics 63(1) 27–42. DOI:10.1007/s40262-023-01339-y PUBMED:https://pubmed.ncbi.nlm.nih.gov/38177893
Pagliano, P, et al., & Ascione, T (2023). Preclinical discovery and development of nirmatrelvir/ritonavir combinational therapy for the treatment of COVID-19 and the lessons learned from SARS-COV-2 variants. Expert opinion on drug discovery 18(12) 1301–1311. DOI:10.1080/17460441.2023.2248879 PUBMED:https://pubmed.ncbi.nlm.nih.gov/37614103
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)