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Pharmacokinetics, mass balance, and metabolism of [C-14]vicagrel, a novel irreversible P2Y(12) inhibitor in humans

文献类型：期刊论文

作者Zheng, Yuan-dong2,3; Zhang, Hua4,5; Zhan, Yan2,3; Bian, Yi-cong4,5; Ma, Sheng4,5; Gan, Hai-xian2; Lai, Xiao-juan6; Liu, Yong-qiang6; Gong, Yan-chun6; Liu, Xue-fang6
刊名ACTA PHARMACOLOGICA SINICA
出版日期2020-11-26
页码12
ISSN号1671-4083
关键词vicagrel [C-14]vicagrel vicagrel pharmacokinetics vicagrel metabolism mass balance P2Y(12) receptor inhibitor
DOI10.1038/s41401-020-00547-7
通讯作者Zhong, Da-fang(dfzhong@simm.ac.cn) ; Miao, Li-yan(miaolysuzhou@163.com) ; Diao, Xing-xing(xxdiao@simm.ac.cn)
英文摘要Vicagrel, a novel irreversible P2Y(12) receptor inhibitor, is undergoing phase III trials for the treatment of acute coronary syndromes in China. In this study, we evaluated the pharmacokinetics, mass balance, and metabolism of vicagrel in six healthy male Chinese subjects after a single oral dose of 20 mg [C-14]vicagrel (120 mu Ci). Vicagrel absorption was fast (T-max = 0.625 h), and the mean t(1/2) of vicagrel-related components was similar to 38.0 h in both plasma and blood. The blood-to-plasma radioactivity AUC(inf) ratio was 0.55, suggesting preferential distribution of drug-related material in plasma. At 168 h after oral administration, the mean cumulative excreted radioactivity was 96.71% of the dose, including 68.03% in urine and 28.67% in feces. A total of 22 metabolites were identified, and the parent vicagrel was not detected in plasma, urine, or feces. The most important metabolic spot of vicagrel was on the thiophene ring. In plasma pretreated with the derivatization reagent, M9-2, which is a methylated metabolite after thiophene ring opening, was the predominant drug-related component, accounting for 39.43% of the radioactivity in pooled AUC(0-8 h) plasma. M4, a mono-oxidation metabolite upon ring-opening, was the most abundant metabolite in urine, accounting for 16.25% of the dose, followed by M3-1, accounting for 12.59% of the dose. By comparison, M21 was the major metabolite in feces, accounting for 6.81% of the dose. Overall, renal elimination plays a crucial role in vicagrel disposition, and the thiophene ring is the predominant metabolic site.
WOS关键词ACTIVE METABOLITE ; CLOPIDOGREL ; VICAGREL ; PRASUGREL ; PLASMA ; PHARMACODYNAMICS ; SINGLE
资助项目Jiangsu Vcare PharmaTech Co., Ltd. ; National Natural Science Foundation of China[81903701] ; National Key New Drug Creation Special Programs[2017ZX09304-021] ; Suzhou Key Laboratory of Drug Clinical Research and Personalized Medicine[SZS201719] ; Special Research Fund of Wu Jieping Medical Foundation of Clinical Pharmacy Branch of Chinese Medical Association[320.6750.19090-50]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000593063100001
源URL[http://119.78.100.183/handle/2S10ELR8/296420]  
专题新药研究国家重点实验室
通讯作者Zhong, Da-fang; Miao, Li-yan; Diao, Xing-xing
作者单位1.Guangzhou JOYO Pharma Ltd, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201210, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Soochow Univ, Dept Clin Pharmacol, Affiliated Hosp 1, Suzhou 215123, Peoples R China
5.Soochow Univ, Inst Interdisciplinary Drug Res & Translat Sci, Suzhou 215006, Peoples R China
6.Jiangsu Vcare PharmaTech Co Ltd, Nanjing 211800, Peoples R China
7.China Pharmaceut Univ, Coll Pharm, State Key Lab Nat Med, Nanjing 210009, Peoples R China
8.China Pharmaceut Univ, Coll Pharm, Ctr Drug Discovery, Nanjing 210009, Peoples R China
推荐引用方式
GB/T 7714		 Zheng, Yuan-dong,Zhang, Hua,Zhan, Yan,et al. Pharmacokinetics, mass balance, and metabolism of [C-14]vicagrel, a novel irreversible P2Y(12) inhibitor in humans[J]. ACTA PHARMACOLOGICA SINICA,2020:12.
APA Zheng, Yuan-dong.,Zhang, Hua.,Zhan, Yan.,Bian, Yi-cong.,Ma, Sheng.,...&Diao, Xing-xing.(2020).Pharmacokinetics, mass balance, and metabolism of [C-14]vicagrel, a novel irreversible P2Y(12) inhibitor in humans.ACTA PHARMACOLOGICA SINICA,12.
MLA Zheng, Yuan-dong,et al."Pharmacokinetics, mass balance, and metabolism of [C-14]vicagrel, a novel irreversible P2Y(12) inhibitor in humans".ACTA PHARMACOLOGICA SINICA (2020):12.

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来源：上海药物研究所

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