key: cord-0996112-a73c9cyl
authors: Austin, Daren; Okour, Malek
title: Evaluation of potential therapeutic options for COVID‐19
date: 2020-05-29
journal: J Clin Pharmacol
DOI: 10.1002/jcph.1669
sha: 6930ade67d110c9da4a017b59872a2d3707b394a
doc_id: 996112
cord_uid: a73c9cyl

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Of note, we find that only four drugs (favipiravir, nitazoxanide, chloroquine and hydroxychloroquine) are predicted to achieve in-vivo average concentrations in excess of in-vitro IC50 values. Three drugs (nitazoxanide, chloroquine and hydroxychloroquine ) are predicted to match IC80s, (defined as 4x IC50), and only hydroxychloroquine to match IC90 (9x IC50). An increased daily dose of 500 mg remdesivir, or 2500 mg niclosamide is also predicted to match in-vitro IC50s in half of patients. At a population level, clinical doses necessary to provide 90% inhibition in at least 90% of patients (as opposed to 50%) are not accessible for any agent except for hydroxychloroquine. Further clinical evaluation of nitazoxanide (1000 mg/day), hydroxychloroquine(620 mg/day), chloroquine (600 mg/day), remdesivir (500 mg/day) and niclosamide (2500 mg/day) appear merited based on in-vitro to in-vivo translational evidence. These clinical studies must be conducted using proper study design (randomized, double blinded…etc) and must assess efficacy and toxicity using appropriate measures and evaluation of safety and tolerability. Caution is additionally advised for agents that are renally cleared, where exposure maybe higher than indicated in our population analysis.

The authors are employees and stockholders of GlaxoSmithKline.

[4] European medicines agency (EMA), Summary on compassionate use, Remdesivir. 03 April 2020. https://www.ema.europa.eu/en/documents/other/summary-compassionate-use-remdesivir-gilead_en.pdf . Accessed on 4/21/2020.

[5] https://www.drugbank.ca/drugs/DB12598#reference-A19227 This article is protected by copyright. All rights reserved. 

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