tetano
Editor, Senior Moderator
Clin Pharmacokinet
. 2020 Jul 28.
doi: 10.1007/s40262-020-00924-9. Online ahead of print.
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
Markus Zeitlinger[SUP] 1 [/SUP], Birgit C P Koch[SUP] 2 [/SUP], Roger Bruggemann[SUP] 3 [/SUP], Pieter De Cock[SUP] 4 [/SUP], Timothy Felton[SUP] 5 6 [/SUP], Maya Hites[SUP] 7 [/SUP], Jennifer Le[SUP] 8 [/SUP], Sonia Luque[SUP] 9 10 [/SUP], Alasdair P MacGowan[SUP] 11 [/SUP], Deborah J E Marriott[SUP] 12 13 [/SUP], Anouk E Muller[SUP] 14 [/SUP], Kristina Nadrah[SUP] 15 16 [/SUP], David L Paterson[SUP] 17 18 [/SUP], Joseph F Standing[SUP] 19 20 [/SUP], Jo?o P Telles[SUP] 21 [/SUP], Michael W?lfl-Duchek[SUP] 22 [/SUP], Michael Thy[SUP] 23 24 [/SUP], Jason A Roberts[SUP] 25 26 27 28 29 [/SUP], PK/PD of Anti-Infectives Study Group (EPASG) of the European Society of Clinical Microbiology, Infectious Diseases (ESCMID)
Affiliations
Abstract
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.
. 2020 Jul 28.
doi: 10.1007/s40262-020-00924-9. Online ahead of print.
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
Markus Zeitlinger[SUP] 1 [/SUP], Birgit C P Koch[SUP] 2 [/SUP], Roger Bruggemann[SUP] 3 [/SUP], Pieter De Cock[SUP] 4 [/SUP], Timothy Felton[SUP] 5 6 [/SUP], Maya Hites[SUP] 7 [/SUP], Jennifer Le[SUP] 8 [/SUP], Sonia Luque[SUP] 9 10 [/SUP], Alasdair P MacGowan[SUP] 11 [/SUP], Deborah J E Marriott[SUP] 12 13 [/SUP], Anouk E Muller[SUP] 14 [/SUP], Kristina Nadrah[SUP] 15 16 [/SUP], David L Paterson[SUP] 17 18 [/SUP], Joseph F Standing[SUP] 19 20 [/SUP], Jo?o P Telles[SUP] 21 [/SUP], Michael W?lfl-Duchek[SUP] 22 [/SUP], Michael Thy[SUP] 23 24 [/SUP], Jason A Roberts[SUP] 25 26 27 28 29 [/SUP], PK/PD of Anti-Infectives Study Group (EPASG) of the European Society of Clinical Microbiology, Infectious Diseases (ESCMID)
Affiliations
- PMID: 32725382
- DOI: 10.1007/s40262-020-00924-9
Abstract
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.