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A double\u2010blind, placebo\u2010controlled, phase I trial was conducted to evaluate the pharmacokinetics (PKs), safety, and tolerability of 10.5\u2010day administration of multiple doses of molnupiravir and its metabolites in healthy, adult participants. Participants were randomly assigned (3:1) to receive molnupiravir (400\u2009mg [<jats:italic>n<\/jats:italic>\u2009=\u20096], 600\u2009mg [<jats:italic>n<\/jats:italic>\u2009=\u20096], and 800\u2009mg [<jats:italic>n<\/jats:italic>\u2009=\u200912]) or matching placebo (<jats:italic>n<\/jats:italic>\u2009=\u20098) every 12\u2009h (q12h) for 10.5\u2009days. Blood was collected to evaluate the PKs of NHC in plasma and of its active metabolite, NHC\u2010triphosphate (NHC\u2010TP), in peripheral blood mononuclear cells (PBMCs). Molnupiravir was generally well\u2010tolerated. All adverse events were mild or moderate in severity and none led to treatment discontinuation. No clinically meaningful dose\u2010related safety findings were observed. Mean time to maximal concentration was ~1.50 to 1.98\u2009h for plasma NHC and ~4.00 to 8.06\u2009h for PBMC NHC\u2010TP. Accumulation was minimal (&lt;1.2) for NHC and ~2\u2010 to 2.5\u2010fold for NHC\u2010TP. Plasma NHC PKs was generally dose proportional, and PBMC NHC\u2010TP PKs was less than dose proportional over the dose range studied. NHC and NHC\u2010TP PK support twice\u2010daily administration. Overall, molnupiravir administered at up to 800\u2009mg q12h for 10.5\u2009days was generally well\u2010tolerated in healthy participants with dose\u2010linear PKs, supporting the evaluation of longer molnupiravir dosing up to 10\u2009days in future clinical trials.<\/jats:p>","DOI":"10.1111\/cts.13602","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T11:53:27Z","timestamp":1690890807000},"page":"1947-1956","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Assessment of pharmacokinetics, safety, and tolerability following <scp>twice\u2010daily<\/scp> administration of molnupiravir for 10\u2009days in healthy participants"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8334-4815","authenticated-orcid":false,"given":"Marian","family":"Iwamoto","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  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