{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T16:55:20Z","timestamp":1772816120297,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Eisai Inc"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lemborexant is a novel orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia. This article describes the population pharmacokinetics (PK) of lemborexant and the relationship of its daily steady\u2010state exposure (C<jats:sub>av,ss<\/jats:sub>) to the probability of most frequent treatment\u2010emergent adverse events (TEAEs). The 12\u00a0230\u2010observation, 1892\u2010subject PK data set included data from 12 clinical studies with predominantly female subjects (66%) ranging in age from 18 to 88 years and from 37 to 168 kg in body weight. The 1664\u2010subject exposure\u2010response data set included data from 3 late\u2010stage studies. Lemborexant pharmacokinetics were described by a 3\u2010compartment model with combined first\u2010 and zero\u2010order absorption with lag time and linear elimination. Oral clearance decreased with increasing body mass index (exponent, \u22120.428), increasing alkaline phosphatase levels (exponent, \u22120.118), and was 26% lower in the elderly (\u226565 years). Across the adverse event analysis, the frequency of subjects experiencing TEAEs during active treatment ranged from approximately 3% to 8%, in the range estimated for placebo. With and without adjustment for age, lemborexant exposure (C<jats:sub>av,ss<\/jats:sub>) was not a clinically meaningful linear predictor of the probability of specific TEAEs: somnolence, nasopharyngitis, flu\/influenza, urinary tract infection, upper respiratory tract infection, or headache. Given the small effect sizes of covariates of the PK model and a low degree of association of lemborexant TEAEs and exposure over the range of phase 3 (therapeutic) 5\u2010 and 10\u2010mg doses, lemborexant can be safely administered without the need for dose adjustment.<\/jats:p>","DOI":"10.1002\/jcph.1683","type":"journal-article","created":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T03:40:08Z","timestamp":1594784408000},"page":"1642-1654","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Population Pharmacokinetics and Exposure\u2010Response Analyses for the Most Frequent Adverse Events Following Treatment With Lemborexant, an Orexin Receptor Antagonist, in Subjects With Insomnia Disorder"],"prefix":"10.1002","volume":"60","author":[{"given":"Bojan","family":"Lalovic","sequence":"first","affiliation":[{"name":"Eisai Inc.  Woodcliff Lake New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oneeb","family":"Majid","sequence":"additional","affiliation":[{"name":"Eisai Ltd.  Hatfield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jagadeesh","family":"Aluri","sequence":"additional","affiliation":[{"name":"Eisai Inc.  Woodcliff Lake New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ishani","family":"Landry","sequence":"additional","affiliation":[{"name":"Eisai Inc.  Woodcliff Lake New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Moline","sequence":"additional","affiliation":[{"name":"Eisai Inc.  Woodcliff Lake New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziad","family":"Hussein","sequence":"additional","affiliation":[{"name":"Eisai Ltd.  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