Hydrolytic Activation and Drug-Drug Interactions of COVID-19 Therapeutics Remdesivir and Molnupiravir: The Role of CES2 Covalent Inhibition and the Impact of Genetic Polymorphism
Shen, Y., Doctoral dissertation, University of Cincinnati
In Vitro and Ex Vivo study showing significant potential drug-drug interactions between remdesivir and molnupiravir. Author found that remdesivir irreversibly inhibits CES2, an enzyme crucial for activating molnupiravir in the body, which may substantially reduce molnupiravir's efficacy. There was considerable individual variations in drug metabolism due to genetic polymorphisms and differing enzyme expression levels across organs. The results suggest that co-administration of remdesivir and molnupiravir should be approached with caution, and that treatment efficacy may vary significantly between individuals.
Shen et al., 3 Aug 2024, peer-reviewed, 1 author.
Ex Vivo studies are an important part of preclinical research, however results may be very different in vivo.
