What Do We Know About Remdesivir Drug Interactions?

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS‐Co‐V‐2) has resulted in a critical need to rapidly develop new pharmacologic interventions and disseminate information. This has led to confusing and conflicting information on drug efficacy. Remdesivir has emerged as a pro...

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Published inClinical and Translational Science Vol. 13; no. 5; pp. 842 - 844
Main Author Yang, Katherine
Format Journal Article Web Resource
LanguageEnglish
Published United States John Wiley & Sons, Inc 01.09.2020
John Wiley and Sons Inc
Wiley
Subjects
Adenosine
Antiviral drugs
Bioavailability
Coronaviruses
COVID-19
DNA-directed RNA polymerase
Epithelial cells
Intracellular
Metabolites
Mortality
Multidrug resistance
Oral administration
Pandemics
Voriconazole
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Abstract The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS‐Co‐V‐2) has resulted in a critical need to rapidly develop new pharmacologic interventions and disseminate information. This has led to confusing and conflicting information on drug efficacy. Remdesivir has emerged as a promising treatment for SARS‐Co‐V‐2 infection yet published clinical pharmacology and drug interaction studies are limited. Additional studies of the disposition of remdesivir, its active metabolite (GS‐441524), and its triphosphate metabolite (GS‐443902) are needed.
AbstractList Since the start of the pandemic, information on potential therapeutic options have been rapidly disseminated on an almost daily basis, often with incomplete or conflicting results and without adequate peer review. Due to the high first‐pass hepatic extraction of phosphoramidates and expected low bioavailability, oral administration of remdesivir was not explored. 9 In respiratory epithelial cells, GS‐441524 is further converted by intracellular esterases into the pharmacologically active nucleoside triphosphate (GS‐443902), which competes with naturally occurring adenosine phosphate and functions as a delayed RNA‐dependent RNA polymerase inhibitor. 7 Although the plasma half‐lives of remdesivir and the intermediate metabolite are short (~ 0.5–1 hour), the plasma and intracellular half‐lives of the GS‐441524 are long (~ 24 and 40 hours, respectively) allowing for once‐daily dosing. Remdesivir is also a weak inhibitor of CYP3A4, OATP1B1, OATP1B3, bile acid export pump, multidrug resistance‐associated protein 4, and sodium‐taurocholate cotransporter protein. According to the website (accessed May 4, 2020), co‐administration of strong CYP3A4 inhibitors, such as voriconazole, is labeled as “no clinically significant interaction expected.”
The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS‐Co‐V‐2) has resulted in a critical need to rapidly develop new pharmacologic interventions and disseminate information. This has led to confusing and conflicting information on drug efficacy. Remdesivir has emerged as a promising treatment for SARS‐Co‐V‐2 infection yet published clinical pharmacology and drug interaction studies are limited. Additional studies of the disposition of remdesivir, its active metabolite (GS‐441524), and its triphosphate metabolite (GS‐443902) are needed.
Author Yang, Katherine
AuthorAffiliation 1 Department of Clinical Pharmacy UCSF School of Pharmacy San Francisco California USA
AuthorAffiliation_xml – name: 1 Department of Clinical Pharmacy UCSF School of Pharmacy San Francisco California USA
Author_xml – sequence: 1
  givenname: Katherine
  surname: Yang
  fullname: Yang, Katherine
  email: katherine.yang2@ucsf.edu
  organization: UCSF School of Pharmacy
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32402130$$D View this record in MEDLINE/PubMed
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Snippet The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS‐Co‐V‐2) has resulted in a critical need to rapidly develop new pharmacologic...
Since the start of the pandemic, information on potential therapeutic options have been rapidly disseminated on an almost daily basis, often with incomplete or...
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SubjectTerms Adenosine
Antiviral drugs
Bioavailability
Coronaviruses
COVID-19
DNA-directed RNA polymerase
Epithelial cells
Intracellular
Metabolites
Mortality
Multidrug resistance
Oral administration
Pandemics
Voriconazole
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Title What Do We Know About Remdesivir Drug Interactions?
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fcts.12815
https://www.ncbi.nlm.nih.gov/pubmed/32402130
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Volume 13
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