A pharmacometric approach to evaluate drugs for potential repurposing as COVID-19 therapeutics

Abstract

Introduction: Developing and evaluating novel compounds for treatment or prophylaxis of emerging infectious diseases is costly and time-consuming. Repurposing of already available marketed compounds is an appealing option as they already have an established safety profile. This approach could substantially reduce cost and time required to make effective treatments available to fight the COVID-19 pandemic. However, this approach is challenging since many drug candidates show efficacy in in vitro experiments, but fail to deliver effect when evaluated in clinical trials. Better approaches to evaluate in vitro data are needed, in order to prioritize drugs for repurposing. Areas covered: This article evaluates potential drugs that might be of interest for repurposing in the treatment of patients with COVID-19 disease. A pharmacometric simulation-based approach was developed to evaluate in vitro activity data in combination with expected clinical drug exposure, in order to evaluate the likelihood of achieving effective concentrations in patients. Expert opinion: The presented pharmacometric approach bridges in vitro activity data to clinically expected drug exposures, and could therefore be a useful compliment to other methods in order to prioritize repurposed drugs for evaluation in prospective randomized controlled clinical trials.