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This combination with a well-known pharmacokinetic enhancer leads to a high risk for drug-drug interactions in a polymedicated elected population for treatment. Six clinical pharmacologists search the scientific literature to provide a first draft of recommendations. Thereafter, twelve other clinical pharmacologists verified the recommendations and proposed modifications. The final draft was then validated by all 18 participants.
They constitute a guideline for primary care situations. Of course, some complex situations may require expert advices and here, again, clinical pharmacologists are at the forefront in providing therapeutic advice. Up to recently, no antiviral treatment was available for the severe acute respiratory syndrome corona virus 2 SARS-CoV-2 infection, particularly during the early phase of infection i. The drug pharmacological mechanism prevents the 11 cleavages performed by M pro on the polyprotein produced by the virus and then blocks its replication cycle.
Nirmatrelvir has shown a good efficacy in preclinical models cellular human bronchial epithelial cells Calu-3 and in murine models with effective concentrations achievable in patients [2] , [3]. In a randomized controlled trial including symptomatic, unvaccinated, non-hospitalized adults at high risk for progression to severe coronavirus disease COVID , nirmatrelvir reduced the incidence of COVID related hospitalization or death by Notably, there was no death in the experimental arm while 13 patients died in the placebo arm [4].
Nirmatrelvir appears, therefore, as a first line option for the treatment of at-risk patients of severe COVID such as elderly patients and those with chronic disease. However, as already observed with HIV-protease inhibitors, nirmatrelvir displays a short half-life, which could result in suboptimal drug exposure and difficulties in achieving efficacy threshold. Indeed, nirmatrelvir is also a substrate of cytochrome P 3A4 isoenzyme CYP3A4 and is extensively metabolized through this pathway, which contributes to the important inter-individual pharmacokinetic variability.
