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

Zeitlinger, Markus (author), Koch, Birgit C. P. (author), Bruggemann, Roger (author), De Cock, Pieter (author), Felton, Timothy (author), Hites, Maya (author), Le, Jennifer (author), Luque, Sonia (author), MacGowan, Alasdair P. (author), Marriott, Deborah J. E. (author), Nadrah, Kristina (author)

There is an urgent need to identify optimal antiviral therapies for COVID-19 caused by SARS-CoV-2. We have conducted a rapid and comprehensive review of relevant pharmacological evidence, focusing on (1) the pharmacokinetics (PK) of potential antiviral therapies; (2) coronavirus-specific pharmacodynamics (PD); (3) PK and PD interactions between proposed combination therapies; (4) pharmacology of major supportive therapies; and (5) 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 remdesivir, the combination of lopinavir/ritonavir (LPV/r) plus ribavirin; and strong evidence for LPV/r plus ribavirin against Middle East Respiratory Syndrome (MERS) for post-exposure prophylaxis in healthcare workers. Despite these emerging data, robust controlled clinical trials assessing patient-centred outcomes remain imperative and clinical data have already reduced expectations with regard to some drugs. Any therapy should be used with caution in the light of potential drug interactions and the uncertainty of optimal doses for treating mild versus serious infections.

• Language: English
• Keywords: SARS-CoV-2, COVID-19, pharmacokinetics, major supportive therapies
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: Str. 1159-1216
• Numbering: Vol. 59, no. 10
• PID: 20.500.12556/RUL-122095
• UDC: 616.9
• ISSN on article: 0312-5963
• DOI: 10.1007/s40262-020-00924-9
• COBISS.SI-ID: 29987331
• Publication date in RUL: 20.11.2020

Record is a part of a journal

• Title: Clinical pharmacokinetics
• Shortened title: Clin. pharmacokinet.
• Publisher: ADIS Press
• ISSN: 0312-5963
• COBISS.SI-ID: 25233152

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.
• Licensing start date: 20.11.2020