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

Kelly E. Duncan; Russ P. Carstens; Kristin L. Butterfield; Yoon Jin; Laura R. Inbody; Andrea K. Schaeffer; Catherine Z. Matthews; Tian Zhao; Shruti Patel; Brian M. Maas; Mickie H. Cheng; S. Aubrey Stoch

doi:10.1111/cts.70073

journal article Open Access Nov 27, 2024

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

Kelly E. Duncan

Russ P. Carstens

Kristin L. Butterfield Yoon Jin Laura R. Inbody Andrea K. Schaeffer Catherine Z. Matthews Tian Zhao

Clinical and Translational Science Vol. 17 No. 12 · Wiley

View at Publisher Save 10.1111/cts.70073

Abstract

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

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Published: Nov 27, 2024
Vol/Issue: 17(12)
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Authors

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Kelly E. Duncan