ArticlePharmaceutical research2023
Physiologically-Based Pharmacokinetic Modeling of PAXLOVID™ with First-Order Absorption Kinetics.
Article in Pharmaceutical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Covid-19: a phase 1, open-label, 3-treatment, 6-sequence, 3-period crossover study to estimate the effect of pf-07321332/ritonavir and ritonavir on the pharmacokinetics of midazolam in healthy participants.
A phase 1, open-label, 3-treatment, 6-sequence, 3-period crossover study to estimate the effect of pf-07321332/ritonavir and ritonavir on the pharmacokinetics of dabigatran in healthy participants
A phase 1, open-label, randomized, single dose, 2 sequence, 2 period crossover study to evaluate the effect of high-fat meal on the relative bioavailability of pf-07321332 boosted with ritonavir in healthy adult participants
A phase 1, open-label, randomized, single-dose, crossover study to estimate the relative bioavailability of pf-07321332 following oral administration of 4 different formulations relative to the commercial tablet formulation in healthy adult participants under fasted conditions
Who cites it
4 citing papers in PubMed, 14 citations in OpenAlex.
- A hybrid ML-PBPK digital twin framework for clinically interpretable readmission risk and drug exposure stratification in diabetes.Frontiers in digital health · 2026Article
- Drug-Drug Interactions between COVID-19 and Tuberculosis Medications: A Comprehensive Review of CYP450 and Transporter-Mediated Effects.Pharmaceuticals (Basel, Switzerland) · 2024Review
- A Comprehensive Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Nirmatrelvir/Ritonavir.Clinical pharmacokinetics · 2024Review
- Safety Profile of Paxlovid in the Treatment of COVID-19.Current pharmaceutical design · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePAXLOVID™ is nirmatrelvir tablets co-packaged with ritonavir tablets. Ritonavir is used as a pharmacokinetics (PK) enhancer to reduce metabolism and increase exposure of nirmatrelvir. This is the first disclosure of Paxlovid physiologically-based pharmacokinetic (PBPK) model.
methodsNirmatrelvir PBPK model with first-order absorption kinetics was developed using in vitro, preclinical, and clinical data of nirmatrelvir in the presence and absence of ritonavir. Clearance and volume of distribution were derived from nirmatrelvir PK obtained using a spray-dried dispersion (SDD) formulation where it is considered to be dosed as an oral solution, and absorption is near complete. The fraction of nirmatrelvir metabolized by CYP3A was estimated based on in vitro and clinical ritonavir drug-drug interaction (DDI) data. First-order absorption parameters were established for both SDD and tablet formulation using clinical data. Nirmatrelvir PBPK model was verified with both single and multiple dose human PK data, as well as DDI studies. Simcyp® first-order ritonavir compound file was also verified with additional clinical data.
resultsThe nirmatrelvir PBPK model described the observed PK profiles of nirmatrelvir well with predicted AUC and C
conclusionsPaxlovid PBPK model developed in this study can be applied to predict PK changes in special populations, as well as model the effect of victim and perpetrator DDI. PBPK modeling continues to play a critical role in accelerating drug discovery and development of potential treatments for devastating diseases such as COVID-19. NCT05263895, NCT05129475, NCT05032950 and NCT05064800.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.