Assessment of pharmacokinetics and tolerability following single‐dose administration of molnupiravir in participants with hepatic or renal impairment

• DOI: 10.1111/cts.70073
• Publication Date: 2024-11-27T09:30:40Z
• Authors: Kelly E. Duncan; Russ P. Carstens; Kristin L. Butter...; Yoon Jin; Laura R. Inbody; Andrea K. Schaeffer; Catherine Z. Matt...; Tian Zhao; Shruti Patel; Brian M. Maas; Mickie H. Cheng; S. Aubrey Stoch
• Keywords: Tolerability

Individuals with chronic liver or kidney disease are at increased risk of severe COVID-19. Molnupiravir is an orally administered antiviral authorized for the treatment mild-to-moderate COVID-19 in adults progression to disease. Two nonrandomized, open-label, single-dose, multicenter, phase 1 trials were conducted investigate effects hepatic and renal impairment on tolerability pharmacokinetics molnupiravir (800 mg) its metabolite β-D-N4-hydroxycytidine (NHC; NCT05386589/NCT05386758). The impact urinary excretion NHC was also assessed. 90% CI geometric mean ratio plasma area under concentration-time curve (AUC) from zero infinity <2.0 participants moderate versus healthy mean-matched controls. Comparable values observed other pharmacokinetic parameters-including AUC 0 12 h, last measurable concentration, peak concentration-in Urinary low impairment; clearance numerically lower those impairment. In both trials, all adverse events mild intensity resolved by study completion. There no clinically relevant treatment-related safety evaluations. Overall, generally well-tolerated, similar profiles participants, supporting use treating these individuals without need dose adjustment.