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.


Journal

Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849

Informations de publication

Date de publication:
10 2020
Historique:
pubmed: 30 7 2020
medline: 31 10 2020
entrez: 30 7 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32725382
doi: 10.1007/s40262-020-00924-9
pii: 10.1007/s40262-020-00924-9
pmc: PMC7385074
doi:

Substances chimiques

Analgesics 0
Anticoagulants 0
Antiviral Agents 0
Hypnotics and Sedatives 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1195-1216

Subventions

Organisme : Medical Research Council
ID : MR/M008665/1
Pays : United Kingdom

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Auteurs

Markus Zeitlinger (M)

Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. markus.zeitlinger@meduniwien.ac.at.

Birgit C P Koch (BCP)

Hospital Pharmacy, Erasmus MC, Rotterdam, The Netherlands.

Roger Bruggemann (R)

Radboud University Medical Center, Nijmegen, The Netherlands.

Pieter De Cock (P)

Department of Pharmacy 2, Heymans Institute of Pharmacology, Ghent University Hospital, Ghent University, Ghent, Belgium.

Timothy Felton (T)

Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
Intensive Care Unit, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.

Maya Hites (M)

Clinic of Infectious Diseases, CUB-Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.

Jennifer Le (J)

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.

Sonia Luque (S)

Pharmacy Department, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain.
Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar D'Investigacions Mèdiques (IMIM), Barcelona, Spain.

Alasdair P MacGowan (AP)

Bristol Centre for Antimicrobial Research and Evaluation, Infection Sciences, Severn Pathology Partnership, North Bristol NHS Trust, Southmead Hospital, Westbury-On-Trym, Bristol, UK.

Deborah J E Marriott (DJE)

St. Vincent's Hospital, Darlinghurst, NSW, Australia.
University of New South Wales, Sydney, NSW, Australia.

Anouk E Muller (AE)

HaaglandenMC, The Hague and ErasmusMC, Rotterdam, The Netherlands.

Kristina Nadrah (K)

Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

David L Paterson (DL)

University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Joseph F Standing (JF)

Infection, Inflammation and Immunity, Great Ormond Street Institute of Child Health, University College London, London, UK.
Department of Pharmacy, Great Ormond Street Hospital for Children, London, UK.

João P Telles (JP)

Department of Infectious Diseases, AC Camargo Cancer Center, São Paulo, SP, Brazil.

Michael Wölfl-Duchek (M)

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.

Michael Thy (M)

Infectious Diseases Department and Intensive Care Unit, Hospital Bichat, Paris, France.
EA7323, Evaluation of Perinatal and Paediatric Therapeutics and Pharmacology, University Paris Descartes, Paris, France.

Jason A Roberts (JA)

University of Queensland Centre for Clinical Research, Faculty of Medicine and Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia. j.roberts2@uq.edu.au.
Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. j.roberts2@uq.edu.au.
Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. j.roberts2@uq.edu.au.
Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France. j.roberts2@uq.edu.au.
The University of Queensland Centre for Clinical Research, The University of Queensland, Royal Brisbane and Women's Hospital, Butterfield St, Herston, QLD, 4029, Australia. j.roberts2@uq.edu.au.

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