Pharmacokinetics/Pharmacodynamics of Antiviral Agents Used to Treat SARS-CoV-2 and Their Potential Interaction with Drug
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REVIEW ARTICLE
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 Zeitlinger1 · Birgit C. P. Koch2 · Roger Bruggemann3 · Pieter De Cock4 · Timothy Felton5,6 · Maya Hites7 · Jennifer Le8 · Sonia Luque9,10 · Alasdair P. MacGowan11 · Deborah J. E. Marriott12,13 · Anouk E. Muller14 · Kristina Nadrah15,16 · David L. Paterson17,18 · Joseph F. Standing19,20 · João P. Telles21 · Michael Wölfl‑Duchek22 · Michael Thy23,24 · Jason A. Roberts25,26,27,28,29 · the PK/PD of Anti-Infectives Study Group (EPASG) of the European Society of Clinical Microbiology, Infectious Diseases (ESCMID)
© The Author(s) 2020
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.
Key Points
On behalf of the PK/PD of Anti-Infectives Study Group (EPASG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID); all authors are affiliated with this group. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40262-020-00924-9) contains supplementary material, which is available to authorized users. * Markus Zeitlinger [email protected] * Jason A. Roberts [email protected] Extended author information available on the last page of the article
The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) PK/PD Study Group has especially convened a group of clinical and PK/ PD experts to provide guidance for all relevant drug therapies for infections caused by the SARS-COV-2 virus. The underlying presents guidance at a high level of detail on the key pharmacokinetic/pharmacodynamic characteristics of drugs at the current most commonly used antiviral regimens, clinically signi
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