Interactions of the Anti-SARS-CoV-2 Agents Molnupiravir and Nirmatrelvir/Paxlovid with Human Drug Transporters

Orally administered small molecules may have important therapeutic potential in treating COVID-19 disease. The recently developed antiviral agents, Molnupiravir and Nirmatrelvir, been reported to be efficient treatments, with only moderate side effects, especially when applied the early phases of this However, drug–drug drug–transporter interactions already noted by drug development companies application notes. In present work, we studied some key human transporters interacting these agents. nucleoside analog (EIDD-2801) its main metabolite (EIDD-1931) were found inhibit CNT1,2 addition ENT1,2 transporters; however, it did not significantly influence relevant OATP or ABCC4 efflux transporter. active component Paxlovid (PF-07321332, Nirmatrelvir) inhibited function several OATPs ABCB1 but affect ABCG2. significant inhibition was observed at high concentrations Nirmatrelvir probably occur vivo. Paxlovid, as used clinic, is a combination (viral protease inhibitor) Ritonavir (a “booster” inhibitor metabolism). known therefore, examined compounds together, ratios. No additional inhibitory effect compared strong transporter caused Ritonavir. Our current vitro results should help estimate newly agents during treatment.