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We investigated the dose\u2013response antiplatelet effects of prasugrel compared with clopidogrel in Japanese patients with non-cardioembolic stroke. The influence of cytochrome P450 (CYP) polymorphisms on the antiplatelet effects of both drugs was also compared. In this multicenter randomized active-control comparative study, patients were randomized to receive prasugrel 2.5\u00a0mg, 5\u00a0mg, or 7.5\u00a0mg (double blind) or clopidogrel 75\u00a0mg (open label) once daily for 14\u00a0days. The primary endpoint was inhibition of platelet aggregation (IPA) in response to adenosine diphosphate 20\u00a0\u03bcM within 8\u00a0h of study drug administration on day\u00a014. Of the 66 patients randomized, data from 63 (prasugrel 2.5\u00a0mg, 5\u00a0mg, and 7.5\u00a0mg groups,<jats:italic>n<\/jats:italic>\u2009=\u200914, 16, and 18, respectively; clopidogrel group,<jats:italic>n<\/jats:italic>\u2009=\u200915) were used in the pharmacodynamic assessment. IPA (arithmetic mean\u2009\u00b1\u2009SD) after prasugrel administration increased dose-dependently (33\u2009\u00b1\u20099%, 44\u2009\u00b1\u200911%, and 53\u2009\u00b1\u200914%, at 2.5\u00a0mg, 5\u00a0mg, and 7.5\u00a0mg, respectively) and was higher in these groups than after clopidogrel (23\u2009\u00b1\u200916%). In a subgroup of CYP2C19 intermediate metabolizers, IPA was higher in the prasugrel 5\u00a0mg and 7.5\u00a0mg groups than in the clopidogrel group. No death or serious adverse events were reported. Prasugrel was well tolerated at doses up to 7.5\u00a0mg\/day and had antiplatelet effects higher than those of clopidogrel 75\u00a0mg\/day. CYP2C19 polymorphisms may have reduced clopidogrel-induced IPA.<\/jats:p>","DOI":"10.1007\/s11239-019-01926-6","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T16:32:44Z","timestamp":1571848364000},"page":"10-17","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial"],"prefix":"10.1007","volume":"49","author":[{"given":"Takenori","family":"Yamaguchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Shirai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yoshiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,23]]},"reference":[{"key":"1926_CR1","volume-title":"Japanese guidelines for the management of stroke 2015","author":"Joint Committee on Guidelines for the Management of Stroke","year":"2015","unstructured":"Joint Committee on Guidelines for the Management of Stroke (2015) Japanese guidelines for the management of stroke 2015. 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