Pharmacokinetics-Pharmacodynamics of Antiviral Agents Used to Treat SARS-CoV-2 and Their Potential Interaction with Drugs and Other Supportive Measures: a Comprehensive Review by the PK/PD of Anti-Infectives Study Group of the European Society of Antimicrobial Agents

Abstract

[enter There is an urgent need to identify optimal antiviral therapies for COVID-19 caused by SARS-CoV-2. We have conducted a rapid comprehensive review to examine antiviral pharmacology evidence, focussing on i) the pharmacokinetics (PK) of available or proposed therapies; ii) coronavirus-specific pharmacodynamics (PD); iii) PK and PD interactions between proposed combination therapies; iv) a review of the pharmacology of major supportive therapies; and v) a summary of anticipated drug-drug interactions (DDIs). We found promising in vitro evidence for remdesivir, (hydroxy)chloroquine and favipiravir against SARS-CoV-2; potential clinical benefit in SARS-CoV-2 with the combination of lopinavir-ritonavir (LPV/r) plus ribavirin; and strong evidence for LPV/r plus ribavirin against MERS for post-exposure prophylaxis in healthcare workers. Despite these emerging data, robust controlled clinical trials remain imperative. These antiviral therapies should be used with caution in the light of the significant drug interactions and the need to evaluate optimal doses for treating mild versus serious infections.

Note: Funding: No funding was received for this manuscript.

Conflict of Interest: The authors declare that they have no conflict of interest associated with the content of the current manuscript.

Keywords: Coronavirus, DDI, Intensive Care, repurposing, off-label, PK/PD, SARS-CoV-2