Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers
文献类型：期刊论文
| 作者 | Li, Xiaojiao5; Liu, Ca6; Zhu, Xiaoxue5; Wei, Haijing5; Zhang, Hong5; Chen, Hong5; Chen, Guiling5; Yang, Deming5; Sun, Hongbin7,8; Shen, Zhenwei3,10 |
| 刊名 | FRONTIERS IN PHARMACOLOGY
 |
| 出版日期 | 2018-06-20 |
| 卷号 | 9 |
| 关键词 | vicagrel pharmacokinetics pharmacodynamics safety clopidogrel |
| ISSN号 | 1663-9812 |
| DOI | 10.3389/fphar.2018.00643 |
| 文献子类 | Article |
| 英文摘要 | Background: Vicagrel is a novel anti platelet drug and hydrolyzed to the same intermediate as clopidogrel via esterase, instead of CYP2C19. Here we report the first clinical trial on the tolerability, pharmacokinetics and pharmacodynamics of different doses of vicagrel, and comparison with clopidogrel in healthy Chinese volunteers. Methods: This study was conducted in two parts. Study I was a dose-escalating (5-15 mg) study. For each dose, 15 participants were randomized into three groups (total = 45); nine participants were given vicagrel, three were given clopidogrel, and three were given a placebo. Study II was conducted to assess interactions between vicagrel and aspirin in 15 healthy participants. The plasma concentrations of the metabolites of vicagrel and clopidogrel were determined using a LC-MS/MS method. Platelet aggregation was assessed using the VerifyNow-P2Y12 assay. Results: Vicagrel (5-15 mg per day) dosing for 10 days or addition of aspirin was well tolerated in healthy volunteers. The exposure of the active metabolite increased proportionally across the dose range and was higher (similar to 10-fold) than clopidogrel. The levels of IPA dosing 75 mg clopidogrel were between the responses of 5 mg and 10 mg vicagrel. After a single loading dose of vicagrel (30 mg) and a once-daily maintenance dose (7.5 mg) for 8 days, the maximum inhibition of platelet aggregation was similar to that seen with the combined use of vicagrel and aspirin (100 mg/day). Conclusion: Oral vicagrel demonstrated a favorable safety profile and excellent anti-platelet activity, which could be a promising P2Y12 antagonist as anti-platelet drug and can be further developed in phase II/III studies, and marketing for the unmet medical needs of cardiovascular diseases. |
| WOS关键词 | ACUTE CORONARY SYNDROMES ; PLATELET-AGGREGATION ; ANTIPLATELET-AGENT ; ACTIVE METABOLITE ; CLINICAL-EFFICACY ; CLOPIDOGREL ; PRASUGREL ; TICAGRELOR ; CARBOXYLESTERASE ; SAFETY |
| 资助项目 | National Major Scientific and Technological Special Project for Significant New Drug Development during the Twelfth Five-Year Plan Period of China[2014ZX09303303] ; Thirteenth Five-Year Plan Period of China[2017ZX09304004] ; Thirteenth Five-Year Plan Period of China[2017ZX09101001002-004] ; National Natural Science Foundation of China[81473037] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000435717100001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279701]  |
| 专题 | 上海药物代谢研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Liu, Bin; Ding, Yanhua |
| 作者单位 | 1.Hun Med Ltd, Shanghai, Peoples R China; 2.Jiangsu Vcare PharmaTech Co Ltd, Nanjing, Jiangsu, Peoples R China; 3.Jilin Univ, Hosp 1, Inst Immunol, Jilin, Jilin, Peoples R China; 4.Jilin Univ, Hosp 1, Dept Hepatol, Jilin, Jilin, Peoples R China; 5.Jilin Univ, Hosp 1, Phase Ciih Trial Unit 1, Jilin, Jilin, Peoples R China; 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China; 7.China Pharmaceut Univ, State Key Lab Nat Med, Nanjing, Jiangsu, Peoples R China; 8.China Pharmaceut Univ, Ctr Drug Discovery, Coll Pharm, Nanjing, Jiangsu, Peoples R China; 9.Jilin Univ, Hosp 1, Dept Hand Surg, Jilin, Jilin, Peoples R China 10.Jilin Univ, Hosp 1, Jilin, Jilin, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Xiaojiao,Liu, Ca,Zhu, Xiaoxue,et al. Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers[J]. FRONTIERS IN PHARMACOLOGY,2018,9. |
| APA | Li, Xiaojiao.,Liu, Ca.,Zhu, Xiaoxue.,Wei, Haijing.,Zhang, Hong.,...&Ding, Yanhua.(2018).Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers.FRONTIERS IN PHARMACOLOGY,9. |
| MLA | Li, Xiaojiao,et al."Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers".FRONTIERS IN PHARMACOLOGY 9(2018). |
入库方式： OAI收割
来源：上海药物研究所
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