Abstract
Nirmatrelvir/ritonavir (N/R) is one of the most effective antiviral drugs against SARS-CoV-2. The preclinical development, pharmacodynamics and pharmacokinetics of N/R are reviewed herein. Randomized clinical trials have been conducted exclusively with pre-Omicron variants of concern, but in vitro studies show that efficacy against all Omicron sublineages is preserved, as confirmed by post-marketing observational studies. Nevertheless, investigations of large viral genome repositories have shown that mutation in the main protease causing resistance to N/R are increasingly frequent. In addition, virological and clinical rebounds after N/R discontinuation have been reported in immunocompetent patients. This finding is of concern when translated to immunocompromised patients, in whom N/R efficacy has not been formally investigated in clinical trials. Economical sustainability and perspectives for this therapeutic arena are discussed.
Original language | English (US) |
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Article number | 106708 |
Journal | International Journal of Antimicrobial Agents |
Volume | 61 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2023 |
Keywords
- Bexovid®
- COVID-19
- PF-00835231
- PF-07321332
- Paxlovid®
- main protease
- nirmatrelvir
- protease inhibitors
- ritonavir
- small-chemical antivirals
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases
- Pharmacology (medical)