{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T15:40:17Z","timestamp":1762875617070},"reference-count":11,"publisher":"Georg Thieme Verlag KG","issue":"09","funder":[{"name":"Daiichi Sankyo Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>\nCYP2C19 genotype has been shown to impact response to clopidogrel 75-mg but not prasugrel 10-mg. Here, we assessed effects of CYP2C19 metaboliser status on pharmacokinetics (PK) and pharmacodynamic (PD) responses to prasugrel 5-mg and 10-mg and clopidogrel 75-mg using data from two PK\/PD studies in stable coronary artery disease (CAD) patients (GENERATIONS and FEATHER). Active metabolite concentrations (area under the curve, AUC[0-tlast]), maximum platelet aggregation (MPA) measured by light transmission aggregometry, vasodilator- stimulated phosphoprotein platelet reactivity index, and VerifyNow P2Y12-platelet reaction units (VN-PRU) were analysed by CYP2C19-predicted phenotype (extensive metaboliser [EM; N=154], *2-*8 non-carriers, vs reduced metaboliser [RM; N=41],*2-*8 carriers\/* 17 non-carriers). AUC(0-tlast) was unaffected by metaboliser status for prasugrel 5-mg and 10-mg (geometric mean EM\/RM ratios 1.00, 95% confidence interval [CI]: 0.86,1.17, p&gt;0.99; and 0.97, 95% CI:0.85,1.12, p=0.71, respectively), but was lower among RMs receiving clopidogrel 75-mg (1.37, 95% CI:1.14,1.65, p&lt;0.001). Platelet reactivity was not significantly affected by CYP2C19 metaboliser status for prasugrel 5-mg, or for prasugrel 10-mg by MPA and VNPRU, but for clopidogrel 75-mg was significantly higher in reduced metabolisers (all measures p&lt;0.01). Prasugrel 10-mg showed greater antiplatelet effects vs clopidogrel 75-mg (all comparisons p&lt;0.001). Prasugrel 5-mg showed greater antiplatelet effects vs clopidogrel 75-mg in RMs (all p&lt;0.001), and comparable effects in EMs (all p\u22650.37). In contrast to clopidogrel, prasugrel active metabolite PK was not influenced by CYP2C19 genotype. Antiplatelet effect for prasugrel 10-mg was greater irrespective of metaboliser status and for prasugrel 5-mg was greater for RMs and comparable for EMs as compared to clopidogrel 75-mg. <\/jats:p>","DOI":"10.1160\/th13-10-0891","type":"journal-article","created":{"date-parts":[[2014,7,10]],"date-time":"2014-07-10T08:29:29Z","timestamp":1404980969000},"page":"589-597","source":"Crossref","is-referenced-by-count":25,"title":["The effect of CYP2C19  gene polymorphisms on the pharmacokinetics and pharmacodynamics of prasugrel 5-mg, prasugrel 10-mg and clopidogrel 75-mg in patients with coronary artery disease"],"prefix":"10.1160","volume":"112","author":[{"given":"Thomas","family":"Bergmeijer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Udaya","family":"Tantry","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurrien","family":"ten Berg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominick","family":"Angiolillo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"James","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas","family":"Lindahl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Svensson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Jakubowski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Brown","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suman","family":"Duvvuru","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Sundseth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Walker","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Small","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Moser","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Winters","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Erlinge","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Gurbel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2017,12,2]]},"reference":[{"key":"10.1160\/TH13-10-0891-1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.851949"},{"key":"10.1160\/TH13-10-0891-2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp157"},{"key":"10.1160\/TH13-10-0891-3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706482"},{"key":"10.1160\/TH13-10-0891-4","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011406280"},{"key":"10.1160\/TH13-10-0891-5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.05.023"},{"key":"10.1160\/TH13-10-0891-6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.08.964"},{"key":"10.1160\/TH13-10-0891-7","doi-asserted-by":"publisher","DOI":"10.1186\/1479-7364-4-4-278"},{"key":"10.1160\/TH13-10-0891-8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0809171"},{"key":"10.1160\/TH13-10-0891-9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61273-1"},{"key":"10.1160\/TH13-10-0891-10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcin.2012.07.015"},{"key":"10.1160\/TH13-10-0891-11","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.12.013"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1160\/TH13-10-0891.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,3,20]],"date-time":"2018-03-20T10:05:35Z","timestamp":1521540335000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1160\/TH13-10-0891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014]]},"references-count":11,"journal-issue":{"issue":"09","published-online":{"date-parts":[[2017,11,22]]},"published-print":{"date-parts":[[2014]]}},"URL":"https:\/\/doi.org\/10.1160\/th13-10-0891","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014]]}}}