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Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit.
Sun, Duxin.
  • Sun D; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, 48109, USA. duxins@umich.edu.
AAPS J ; 22(4): 77, 2020 05 26.
Article in English | MEDLINE | ID: covidwho-377941
ABSTRACT
Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5-9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. Graphical abstract.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Pneumonia, Viral / Adenosine Monophosphate / Coronavirus Infections / Alanine / Betacoronavirus Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: AAPS J Journal subject: Pharmacology / Drug Therapy Year: 2020 Document Type: Article Affiliation country: S12248-020-00459-8

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Pneumonia, Viral / Adenosine Monophosphate / Coronavirus Infections / Alanine / Betacoronavirus Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: AAPS J Journal subject: Pharmacology / Drug Therapy Year: 2020 Document Type: Article Affiliation country: S12248-020-00459-8