Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y12inhibitor
文献类型：期刊论文
| 作者 | Zhang, Yifan1 ; Zhu, Xiaoxue2; Zhan, Yan1; Li, Xiaojiao2; Liu, Cai1; Zhu, Yunting1; Zhang, Hong2; Wei, Haijing2; Xia, Yu1; Sun, Hongbin3,4
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| 刊名 | BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
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| 出版日期 | 2020-04-08 |
| 卷号 | 86期号:9页码:1860-1874 |
| 关键词 | P2Y(12)inhibitor pharmacodynamics pharmacokinetics vicagrel |
| ISSN号 | 0306-5251 |
| DOI | 10.1111/bcp.14296 |
| 文献子类 | Article |
| 英文摘要 | Aims We investigated the impacts of CYP2C19 polymorphisms on pharmacokinetics and pharmacodynamics of vicagrel in healthy Chinese subjects. Methods CYP2C19 extensive metabolizers (EMs), intermediate metabolizers (IMs) and poor metabolizers (PMs; 16 subjects/group) participated in a randomized, open-label, 2-period cross-over study. Each study period lasted 7 days, with a loading dose of 24 mg of vicagrel or 300 mg of clopidogrel on day 1, and maintenance doses of 6 mg of vicagrel or 75 mg of clopidogrel daily from day 2 to day 7. The pharmacokinetics and pharmacodynamics were assessed on day 1 and day 7. Results After a loading dose, the AUC(0-t)of the active metabolite H4 by vicagrel was slightly lower in IMs and PMs (decreased by 21 and 27%, respectively) compared to EMs. Similar results were found after maintenance doses. In EMs, the AUC(0-t)of H4 by vicagrel was somewhat higher than clopidogrel after the loading dose, and comparable with clopidogrel (90% confidence interval 0.94, 1.21) after the maintenance doses. However, it was much higher than clopidogrel in PMs, with a 1.28-fold (loading dose) and a 73% (maintenance doses) increases compared to clopidogrel (P< 0.001). Consequently, the inhibition of platelet aggregation by vicagrel was greater than clopidogrel after both loading dose (28.2vs12.4% at 4 hours,P< 0.01) and maintenance doses (42.8vs24.6% at 4 hours,P< 0.001) in PMs. Conclusions CYP2C19 polymorphisms have less impact on vicagrel as compared to clopidogrel. Drug exposure and response to vicagrel in PMs were even higher than to clopidogrel in IMs. |
| WOS关键词 | ST-SEGMENT ELEVATION ; CLOPIDOGREL BIOACTIVATION ; ACTIVE METABOLITE ; MYOCARDIAL-INFARCTION ; PHARMACOKINETICS ; CHINESE ; PHARMACODYNAMICS ; RESISTANCE ; COMMON ; GUIDELINES |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000540474300001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309413]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Yifan; Zhu, Xiaoxue; Zhong, Dafang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai, Peoples R China; 2.Jilin Univ, Hosp 1, Phase Clin Trial Unit 1, 71 Xinmin St, Changchun, Jilin, Peoples R China; 3.China Pharmaceut Univ, Coll Pharm, State Key Lab Nat Med, Nanjing, Peoples R China; 4.China Pharmaceut Univ, Coll Pharm, Ctr Drug Discovery, Nanjing, Peoples R China; 5.Jiangsu Vcare PharmaTech Co Ltd, Nanjing, Peoples R China; 6.Hua Med Ltd, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Yifan,Zhu, Xiaoxue,Zhan, Yan,et al. Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y12inhibitor[J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY,2020,86(9):1860-1874. |
| APA | Zhang, Yifan.,Zhu, Xiaoxue.,Zhan, Yan.,Li, Xiaojiao.,Liu, Cai.,...&Zhong, Dafang.(2020).Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y12inhibitor.BRITISH JOURNAL OF CLINICAL PHARMACOLOGY,86(9),1860-1874. |
| MLA | Zhang, Yifan,et al."Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y12inhibitor".BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 86.9(2020):1860-1874. |
入库方式： OAI收割
来源：上海药物研究所
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