Journal Article

Pharmacokinetics and Safety of Single and Multiple Doses of Molnupiravir in Healthy Male Chinese Adults: An Open‐Label, Fixed Sequence, Phase 1 Study

Zhu, Jixiang, Cheng, Mickie H., Sun, Fang, Zang, Yanqiao, Li, Haiyan, Zhang, Danning, Liu, Zhiping, Yan, Bei, Stoch, S. Aubrey, Maas, Brian M., Zhao, Weiwei

2026

Overview

Molnupiravir is an orally administered prodrug of β‐D‐N4‐hydroxycytidine (NHC) that is conditionally approved in China for the treatment of mild to moderate COVID‐19 in nonhospitalized adults at high risk of disease progression. Molnupiravir is rapidly absorbed and hydrolyzed to deliver NHC into systemic circulation. An open‐label, fixed‐sequence, Phase 1 study was conducted to evaluate the tolerability, safety, and pharmacokinetics (PK) following single and multiple (every 12 h for 5.5 days) oral dosing of molnupiravir 800 mg in 16 healthy, male Chinese participants. After multiple doses of molnupiravir, the median time to maximum concentration was 2.0 h for plasma NHC. NHC concentrations generally decreased in a biphasic manner, with a terminal half‐life of 21.9 h, and NHC exposures (i.e., area under the curve and maximum plasma concentration) were similar following single and multiple doses of molnupiravir. No accumulation of NHC in plasma was observed. When compared with historical data from published clinical trials of similar study design, NHC exposure in Chinese participants was marginally higher than that in non‐Asian participants but remained within established clinical bounds. Overall, molnupiravir was generally well‐tolerated. Ten participants (63.5%) experienced at least one adverse event throughout the study, the severity of which was mild or moderate, and none led to treatment discontinuation. There were no clinically meaningful findings in other safety evaluations. These data support use of the standard 5‐day regimen of molnupiravir 800 mg every 12 h without dose adjustment for the treatment of COVID‐19 in the Chinese population. Study Highlights What is the current knowledge on the topic? ○Molnupiravir is an orally administered prodrug of β‐D‐N4‐hydroxycytidine (NHC) with potent, broad‐spectrum preclinical activity against RNA viruses, including SARS‐CoV‐2, and a high barrier to the development of resistance. ○Molnupiravir is conditionally approved in China for the treatment of mild to moderate COVID‐19 in nonhospitalized adults at high risk of disease progression. ○The safety and pharmacokinetics (PK) of molnupiravir have been extensively studied in clinical trials in which healthy volunteers and patients with COVID‐19 were enrolled. ○Tolerability and PK data in Asian populations are limited. What question did this study address? ○An open‐label, fixed‐sequence, Phase 1 study was conducted to evaluate the tolerability, safety, and PK following single and multiple (every 12 h for 5.5 days) oral dosing of molnupiravir 800 mg in 16 healthy, male Chinese participants. What does this study add to our knowledge? ○Molnupiravir was generally well tolerated in healthy Chinese participants; all adverse events were mild or moderate in severity, and none resulted in treatment discontinuation. ○NHC concentrations generally decreased in a biphasic manner and NHC exposures were similar following single and multiple doses of molnupiravir in healthy Chinese participants; no accumulation of NHC in plasma was observed. ○The NHC exposure observed in Chinese participants was marginally higher than the exposure previously reported in non‐Asian individuals but remained within the established clinical bounds for NHC. How might this change clinical pharmacology or translational science? ○These results support the use of the standard regimen of molnupiravir for the treatment of COVID‐19 (i.e., 800 mg every 12 h for 5 days) in the Chinese population without the need for dose adjustment.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Administration, Oral / Adult / antiviral / Antiviral Agents - administration & dosage / Antiviral Agents - adverse effects / Antiviral Agents - pharmacokinetics / Area Under Curve / China / Clinical trials / COVID-19 / COVID-19 Drug Treatment / Cytidine - administration & dosage / Cytidine - adverse effects / Cytidine - analogs & derivatives / Cytidine - pharmacokinetics / Disease progression / Dosage / Drug Administration Schedule / Drug dosages / East Asian People / Genomes / Healthy Volunteers / Humans / Hydroxylamines - administration & dosage / Hydroxylamines - adverse effects / Hydroxylamines - pharmacokinetics / Male / Middle Aged / Oral administration / Pharmacokinetics / phase 1 / Plasma / ribonucleoside analog / Risk assessment / SARS‐CoV‐2 / Severe acute respiratory syndrome coronavirus 2 / Young Adult / β‐D‐N4‐hydroxycytidine