Nirmatrelvir/ritonavir (N/R) is one of the most effective antiviral drugs against SARS-CoV-2. The preclini-cal development, pharmacodynamics and pharmacokinetics of N/R are reviewed herein. Randomized clin-ical 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 observa-tional 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 clin-ical 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 for-mally investigated in clinical trials. Economical sustainability and perspectives for this therapeutic arena are discussed. (c) 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Nirmatrelvir and COVID-19: development, pharmacokinetics, clinical efficacy, resistance, relapse, and pharmacoeconomics / Focosi, D.; Mcconnell, S.; Shoham, S.; Casadevall, A.; Maggi, F.; Antonelli, G.. - In: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS. - ISSN 0924-8579. - 61:2(2023), p. 106708. [10.1016/j.ijantimicag.2022.106708]

Nirmatrelvir and COVID-19: development, pharmacokinetics, clinical efficacy, resistance, relapse, and pharmacoeconomics

Antonelli G.
2023

Abstract

Nirmatrelvir/ritonavir (N/R) is one of the most effective antiviral drugs against SARS-CoV-2. The preclini-cal development, pharmacodynamics and pharmacokinetics of N/R are reviewed herein. Randomized clin-ical 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 observa-tional 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 clin-ical 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 for-mally investigated in clinical trials. Economical sustainability and perspectives for this therapeutic arena are discussed. (c) 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.
2023
Bexovid®; COVID-19; PF-00835231; PF-07321332; Paxlovid®; main protease; nirmatrelvir; protease inhibitors; ritonavir; small-chemical antivirals
01 Pubblicazione su rivista::01g Articolo di rassegna (Review)
Nirmatrelvir and COVID-19: development, pharmacokinetics, clinical efficacy, resistance, relapse, and pharmacoeconomics / Focosi, D.; Mcconnell, S.; Shoham, S.; Casadevall, A.; Maggi, F.; Antonelli, G.. - In: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS. - ISSN 0924-8579. - 61:2(2023), p. 106708. [10.1016/j.ijantimicag.2022.106708]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1680311
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 18
social impact