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

187 Pages Posted: 10 Apr 2020

See all articles by Markus Zeitlinger

Markus Zeitlinger

Medical University of Vienna - Department of Clinical Pharmacology

Birgit CP Koch

Erasmus University Rotterdam (EUR) - Erasmus Medical Center (MC)

Roger Brüggemann

Radboud University Nijmegen - Radboud University Medical Center

Pieter De Cock

Ghent University - Ghent University Hospital

Timothy Felton

The University of Manchester

Maya Hites

Université Libre de Bruxelles (ULB)

Jennifer Le

University of California, San Diego (UCSD) - Skaggs School of Pharmacy and Pharmaceutical Sciences

Sonia Luque

Hospital del Mar

Alasdair MacGowan

Southmead Hospital - Bristol Centre for Antimicrobial Research & Evaluation (BCARE)

Deborah Marriott

University of New South Wales (UNSW) - St Vincent’s Hospital

Anouk E Muller

Erasmus University Rotterdam (EUR) - Erasmus Medical Center (MC)

Kristina Nadrah

University of Ljubljana - University Medical Centre Ljubljana

David Paterson

University of Queensland

Joseph F. Standing

University College London - Department of Infection, Inflammation and Immunity; Great Ormond Street Hospital for Children - Department of Pharmacy

João P. Telles

A.C. Camargo Cancer Center

Michael Wölfl-Duchek

Medical University of Vienna

Michael Thy

Hopital Bichat Claude Bernard

Jason A. Roberts

University of Queensland

Date Written: March 23, 2020

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

Suggested Citation

Zeitlinger, Markus and Koch, Birgit CP and Brüggemann, Roger and De Cock, Pieter and Felton, Timothy and Hites, Maya and Le, Jennifer and Luque, Sonia and MacGowan, Alasdair and Marriott, Deborah and Muller, Anouk E and Nadrah, Kristina and Paterson, David and Standing, Joseph F. and Telles, João P. and Wölfl-Duchek, Michael and Thy, Michael and Roberts, Jason A., 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 (March 23, 2020). Available at SSRN: https://ssrn.com/abstract=3561236 or http://dx.doi.org/10.2139/ssrn.3561236

Markus Zeitlinger (Contact Author)

Medical University of Vienna - Department of Clinical Pharmacology ( email )

Birgit CP Koch

Erasmus University Rotterdam (EUR) - Erasmus Medical Center (MC)

Doctor Molewaterplein 40
Rotterdam, South Holland 3015 GD
Netherlands

Roger Brüggemann

Radboud University Nijmegen - Radboud University Medical Center

Geert Grooteplein Zuid 10
Nijmegen
Netherlands

Pieter De Cock

Ghent University - Ghent University Hospital

Belgium

Timothy Felton

The University of Manchester

Oxford Road
Manchester, N/A M13 9PL
United Kingdom

Maya Hites

Université Libre de Bruxelles (ULB)

CP 132 Av FD Roosevelt 50
Brussels, Brussels 1050
Belgium

Jennifer Le

University of California, San Diego (UCSD) - Skaggs School of Pharmacy and Pharmaceutical Sciences

La Jolla, CA
United States

Sonia Luque

Hospital del Mar

Barcelona
Spain

Alasdair MacGowan

Southmead Hospital - Bristol Centre for Antimicrobial Research & Evaluation (BCARE) ( email )

Deborah Marriott

University of New South Wales (UNSW) - St Vincent’s Hospital ( email )

390 Victoria St
Darlinghurst, Sydney NSW 2010
Australia

Anouk E Muller

Erasmus University Rotterdam (EUR) - Erasmus Medical Center (MC)

Doctor Molewaterplein 40
Rotterdam, South Holland 3015 GD
Netherlands

Kristina Nadrah

University of Ljubljana - University Medical Centre Ljubljana

Zaloška cesta 7
1000 Ljubljana
Slovenia

David Paterson

University of Queensland

St Lucia
Brisbane, Queensland 4072
Australia

Joseph F. Standing

University College London - Department of Infection, Inflammation and Immunity ( email )

30 Guilford Street
London
United Kingdom

Great Ormond Street Hospital for Children - Department of Pharmacy ( email )

London
United Kingdom

João P. Telles

A.C. Camargo Cancer Center

São Paulo-SP
Brazil

Michael Wölfl-Duchek

Medical University of Vienna

Vienna
Austria

Michael Thy

Hopital Bichat Claude Bernard

Paris
France

Jason A. Roberts

University of Queensland ( email )

St Lucia
Brisbane, Queensland 4072
Australia

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