{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:20:59Z","timestamp":1791091259072,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,12,8]],"date-time":"2011-12-08T00:00:00Z","timestamp":1323302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>Observations from clinical studies have demonstrated that:<\/jats:p><jats:p>\u2022\u2003CYP2C19 genotype does not have a clinically relevant effect on active metabolite concentrations or platelet inhibition in prasugrel\u2010treated subjects.<\/jats:p><jats:p>\u2022\u2003Variability of response to clopidogrel is related to the presence of reduced function CYP2C19 alleles.<\/jats:p><jats:p>\u2022\u2003Lower concentrations of clopidogrel active metabolite and reduced platelet inhibition lead to increased adverse cardiovascular events in patients with acute coronary syndromes.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Observations from previous studies related to the effect of CYP2C19 genotype on plasma drug exposure and platelet response to prasugrel and clopidogrel are confirmed in this prospectively\u2010stratified, randomized, crossover, genetic study in healthy Chinese subjects.<\/jats:p><jats:p>\u2022\u2003In this study, healthy subjects receiving prasugrel had higher exposure to its active metabolite and greater pharmacodynamic responses (inhibition of platelet aggregation) compared with clopidogrel treated subjects, regardless of CYP2C19\u2010predicted phenotype group.<\/jats:p><jats:p>\u2022\u2003The exposure to the active metabolite of clopidogrel was lower in CYP2C19 IM compared with RM, and in CYP2C19 PM compared with IM. The inhibition of platelet aggregation was lowest in clopidogrel treated CYP2C19 PM subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>AIMS<\/jats:title><jats:p>This open\u2010label, two\u2010period, randomized, crossover study was designed to determine the effect of CYP2C19 reduced function variants on exposure to active metabolites of, and platelet response to, prasugrel and clopidogrel.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Ninety healthy Chinese subjects, stratified by CYP2C19 phenotype, were randomly assigned to treatment with prasugrel 10\u2003mg or clopidogrel 75\u2003mg for 10 days followed by 14 day washout and 10 day treatment with the other drug. Eighty\u2010three subjects completed both treatment periods. Blood samples were collected at specified time points for measurement of each drug's active metabolite (Pras\u2010AM and Clop\u2010AM) concentrations and determination of inhibition of platelet aggregation (IPA) by light transmittance aggregometry. CYP2C19 genotypes were classified into three predicted phenotype groups: rapid metabolizers [RMs (*1\/*1)], heterozygous or intermediate metabolizers [IMs (*1\/*2, *1\/*3)] and poor metabolizers [PMs (*2\/*2, *2\/*3)].<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Pras\u2010AM exposure was similar in IMs and RMs (90% CI 0.85, 1.03) and slightly lower in PMs than IMs (90% CI 0.74, 0.99), whereas Clop\u2010AM exposure was significantly lower in IMs compared with RMs (90% CI 0.62, 0.83), and in PMs compared with IMs (90% CI 0.53, 0.82). IPA was more consistent among RMs, IMs and PMs in prasugrel treated subjects (80.2%, 84.2% and 80.2%, respectively) than in clopidogrel treated subjects (59.7%, 56.2% and 36.8%, respectively; <jats:italic>P<\/jats:italic> &lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Prasugrel demonstrated higher active metabolite exposure and more consistent pharmacodynamic response across all three predicted phenotype groups compared with clopidogrel, confirming observations from previous research that CYP2C19 phenotype plays an important role in variability of response to clopidogrel, but has no impact on response to prasugrel.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2011.04049.x","type":"journal-article","created":{"date-parts":[[2011,6,21]],"date-time":"2011-06-21T04:15:05Z","timestamp":1308629705000},"page":"93-105","source":"Crossref","is-referenced-by-count":38,"title":["Pharmacokinetics and pharmacodynamics following maintenance doses of prasugrel and clopidogrel in Chinese carriers of CYP2C19 variants"],"prefix":"10.1111","volume":"73","author":[{"given":"Ronan P.","family":"Kelly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra L.","family":"Close","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagy A.","family":"Farid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Winters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanni","family":"Natanegara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Jakubowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Small","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,8]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009343005"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.007989"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.029132"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61273-1"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.014522"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.020248"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e3181492209"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02598.x"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2006.10.010"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03809.x"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-013052"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02775.x"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02722.x"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.20"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0809171"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.851949"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.11.048"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp157"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808227"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1008410"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.885194"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2005.10.002"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2010.21"},{"key":"e_1_2_7_25_2","unstructured":"Bristol\u2010Myers Squibb\/Sanofi Pharmaceuticals Partnership [Internet].Plavix\u00ae (clopidogrel bisulfate) tablets: highlights of prescribing information. 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