Drugs in COVID-19 Clinical Trials: Predicting Transporter-Mediated Drug-Drug Interactions Using In Vitro Assays and Real-World Data.

Autor: Yee SW; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA., Vora B; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA., Oskotsky T; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California, USA., Zou L; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA., Jakobsen S; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA., Enogieru OJ; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA., Koleske ML; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA., Kosti I; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California, USA., Rödin M; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA., Sirota M; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California, USA., Giacomini KM; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2021 Jul; Vol. 110 (1), pp. 108-122. Date of Electronic Publication: 2021 May 03.
DOI: 10.1002/cpt.2236
Abstrakt: Numerous drugs are currently under accelerated clinical investigation for the treatment of coronavirus disease 2019 (COVID-19); however, well-established safety and efficacy data for these drugs are limited. The goal of this study was to predict the potential of 25 small molecule drugs in clinical trials for COVID-19 to cause clinically relevant drug-drug interactions (DDIs), which could lead to potential adverse drug reactions (ADRs) with the use of concomitant medications. We focused on 11 transporters, which are targets for DDIs. In vitro potency studies in membrane vesicles or HEK293 cells expressing the transporters coupled with DDI risk assessment methods revealed that 20 of the 25 drugs met the criteria from regulatory authorities to trigger consideration of a DDI clinical trial. Analyses of real-world data from electronic health records, including a database representing nearly 120,000 patients with COVID-19, were consistent with several of the drugs causing transporter-mediated DDIs (e.g., sildenafil, chloroquine, and hydroxychloroquine). This study suggests that patients with COVID-19, who are often older and on various concomitant medications, should be carefully monitored for ADRs. Future clinical studies are needed to determine whether the drugs that are predicted to inhibit transporters at clinically relevant concentrations, actually result in DDIs.
(© 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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