TY - JOUR
T1 - Pharmacokinetics/Pharmacodynamics of Antiviral Agents Used to Treat SARS-CoV-2 and Their Potential Interaction with Drugs and Other Supportive Measures
T2 - A Comprehensive Review by the PK/PD of Anti-Infectives Study Group of the European Society of Antimicrobial Agents
AU - PK/PD of Anti-Infectives Study Group (EPASG) of the European Society of Clinical Microbiology, Infectious Diseases (ESCMID)
AU - Zeitlinger, Markus
AU - Koch, Birgit C P
AU - Bruggemann, Roger
AU - De Cock, Pieter
AU - Felton, Timothy
AU - Hites, Maya
AU - Le, Jennifer
AU - Luque, Sonia
AU - MacGowan, Alasdair P
AU - Marriott, Deborah J E
AU - Muller, Anouk E
AU - Nadrah, Kristina
AU - Paterson, David L
AU - Standing, Joseph F
AU - Telles, João P
AU - Wölfl-Duchek, Michael
AU - Thy, Michael
AU - Roberts, Jason A
N1 - Funding Information:
Open access funding provided by Medical University of Vienna. This review was performed by members of the PK/PD of Anti-Infectives Study Group (EPASG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). JFS was funded by a United Kingdom Medical Research Council Fellowship (MR/M008665/1). JAR would like to acknowledge funding from the Australian National Health and Medical Research Council for a Centre of Research Excellence (APP1099452) and a Practitioner Fellowship (APP1117065).
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
KW - Analgesics/pharmacology
KW - Anticoagulants/pharmacology
KW - Antiviral Agents/pharmacokinetics
KW - Betacoronavirus
KW - Coronavirus Infections/drug therapy
KW - Dose-Response Relationship, Drug
KW - Drug Interactions
KW - Extracorporeal Membrane Oxygenation/methods
KW - Humans
KW - Hypnotics and Sedatives/pharmacology
KW - Pandemics
KW - Pneumonia, Viral/drug therapy
KW - Renal Replacement Therapy/methods
KW - Therapeutic Index, Drug
U2 - 10.1007/s40262-020-00924-9
DO - 10.1007/s40262-020-00924-9
M3 - Article
C2 - 32725382
SN - 0312-5963
VL - 59
SP - 1195
EP - 1216
JO - Clinical Pharmacokinetics
JF - Clinical Pharmacokinetics
IS - 10
ER -