{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:14:58Z","timestamp":1791357298122,"version":"4.3.1"},"reference-count":13,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T00:00:00Z","timestamp":1501113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Brexpiprazole is currently approved in the United States for the treatment of schizophrenia and as adjunctive treatment of major depressive disorder. In Canada, it is approved for the treatment of schizophrenia. This study evaluated the pharmacokinetics (PK) and safety of brexpiprazole in Japanese patients with schizophrenia. This phase 1 study comprised a 14\u2010day multiple\u2010dose administration of brexpiprazole 1, 4, and 6 mg\/day (n = 7, 8, and 6, respectively). Plasma concentrations and PK parameters and the influence of <jats:italic>CYP2D6<\/jats:italic> polymorphisms (intermediate metabolizers [IMs] and extensive metabolizers [EMs]) on PK were evaluated. Adverse events (AEs) were recorded. The C<jats:sub>max<\/jats:sub> and AUC<jats:sub>24h<\/jats:sub> of brexpiprazole and its metabolite, DM\u20103411, showed dose\u2010proportionality. The C<jats:sub>max<\/jats:sub> and AUC<jats:sub>24h<\/jats:sub> of brexpiprazole showed accumulation of about 2.5\u2010 to 5.5\u2010fold on day 14, compared with those on day 1. The median t<jats:sub>max<\/jats:sub> and the mean elimination half\u2010life of brexpiprazole were 4\u20135 and 52\u201392 hours, respectively, across all doses on day 14. The C<jats:sub>24h<\/jats:sub> of brexpiprazole reached steady state after day 10 in all dose groups. The dose\u2010normalized C<jats:sub>max<\/jats:sub> and AUC<jats:sub>24h<\/jats:sub> of brexpiprazole on day 14 were higher in IM patients than in EM patients. AEs were generally mild to moderate, with transient serum prolactin increase being the most common event. No clinically significant changes were observed for other clinical laboratory values. Brexpiprazole was safe and well tolerated in the studied Japanese patients with schizophrenia.<\/jats:p>","DOI":"10.1002\/jcph.979","type":"journal-article","created":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T18:56:49Z","timestamp":1501181809000},"page":"74-80","source":"Crossref","is-referenced-by-count":36,"title":["Pharmacokinetics and Safety of Brexpiprazole Following Multiple\u2010Dose Administration to Japanese Patients With Schizophrenia"],"prefix":"10.1002","volume":"58","author":[{"given":"Jun","family":"Ishigooka","sequence":"first","affiliation":[{"name":"Institute of CNS Pharmacology Shibuya\u2010ku  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Iwashita","sequence":"additional","affiliation":[{"name":"Headquarters of Clinical Development Otsuka Pharmaceutical Co. Ltd., Chuo\u2010ku  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koushi","family":"Higashi","sequence":"additional","affiliation":[{"name":"Headquarters of Clinical Development Otsuka Pharmaceutical Co. Ltd., Chuo\u2010ku  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ei Leen","family":"Liew","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs Otsuka Pharmaceutical Co. Ltd., Minato\u2010ku  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Tadori","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs Otsuka Pharmaceutical Co. Ltd., Minato\u2010ku  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-9338(10)71701-6"},{"key":"e_1_2_9_3_1","unstructured":"Abilify Prescribing Information. Otsuka Pharmaceutical Co Ltd.;2016."},{"key":"e_1_2_9_4_1","unstructured":"Otsuka Pharmaceutical Co Ltd. Prescribing Information for Rexulti\u00ae(brexpiprazole) tablets.2015.http:\/\/www.accessdata.fda.gov."},{"key":"e_1_2_9_5_1","unstructured":"Otsuka Pharmaceutical Co Ltd. 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