{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:09:49Z","timestamp":1785434989045,"version":"3.56.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006453","name":"Taisho Toyama Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Vornorexant is a novel dual orexin receptor antagonist (DORA) for the treatment of insomnia with a short elimination half\u2010life. Estimation of the human orexin receptor occupancy can provide insight into the duration of the sleep\u2010promoting effect of DORAs. Herein, we developed a pharmacokinetic\u2010receptor occupancy (PK\/RO) model for OX\n                    <jats:sub>1<\/jats:sub>\n                    and OX\n                    <jats:sub>2<\/jats:sub>\n                    receptors in rats and estimated their receptor occupancy in humans based on the human plasma concentrations after oral administration of vornorexant. The estimated occupancy of the human OX\n                    <jats:sub>2<\/jats:sub>\n                    receptor, which is primarily involved in sleep induction, exceeded 70% at 30\u2009min after dosing of therapeutic doses of 5 and 10\u2009mg. The human OX\n                    <jats:sub>2<\/jats:sub>\n                    receptor occupancy at 6\u2009h post\u2010dose of 5 and 10\u2009mg was estimated to be approximately 50% and 60%, respectively, comparable to the occupancy necessary to exert sleep\u2010promoting effects in rats. Occupancy of the human OX\n                    <jats:sub>1<\/jats:sub>\n                    receptor by vornorexant was higher than that of the OX\n                    <jats:sub>2<\/jats:sub>\n                    receptor. The estimated human OX\n                    <jats:sub>1<\/jats:sub>\n                    and OX\n                    <jats:sub>2<\/jats:sub>\n                    receptor occupancy decreased with short half\u2010lives depending on the plasma concentration. These results suggest that vornorexant exerts rapid sleep\u2010promoting effects and maintains sleep for at least 6\u2009h, and these estimations of the OX\n                    <jats:sub>2<\/jats:sub>\n                    receptor occupancy could support the clinical results. Vornorexant may have a favorable PK\/RO profile for rapid sleep onset and sufficient sleep maintenance with minimal next\u2010day residual effects in humans.\n                  <\/jats:p>","DOI":"10.1002\/prp2.70217","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T05:41:21Z","timestamp":1770010881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Estimation of the Orexin Receptor Occupancy From Human Plasma Pharmacokinetics of Vornorexant, a Novel Dual Orexin 1\/2 Receptor Antagonist for the Treatment of Insomnia"],"prefix":"10.1002","volume":"14","author":[{"given":"Shunsuke","family":"Kamigaso","sequence":"first","affiliation":[{"name":"Research Center Taisho Pharmaceutical Co., Ltd.  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7936-5890","authenticated-orcid":false,"given":"Yoshihiro","family":"Konno","sequence":"additional","affiliation":[{"name":"Research Center Taisho Pharmaceutical Co., Ltd.  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohiko","family":"Hikichi","sequence":"additional","affiliation":[{"name":"Research Center Taisho Pharmaceutical Co., Ltd.  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-3554","authenticated-orcid":false,"given":"Daiji","family":"Kambe","sequence":"additional","affiliation":[{"name":"Development Headquarters Taisho Pharmaceutical Co., Ltd.  Toshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Mano","sequence":"additional","affiliation":[{"name":"Development Headquarters Taisho Pharmaceutical Co., Ltd.  Toshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Tokumaru","sequence":"additional","affiliation":[{"name":"Research Center Taisho Pharmaceutical Co., Ltd.  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruyuki","family":"Mori","sequence":"additional","affiliation":[{"name":"Development Headquarters Taisho Pharmaceutical Co., Ltd.  Toshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Development Headquarters Taisho Pharmaceutical Co., Ltd.  Toshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Chino","sequence":"additional","affiliation":[{"name":"Development Headquarters Taisho Pharmaceutical Co., Ltd.  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