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Pharmacokinetics, mass balance, and metabolism of [14C]vicagrel, a novel irreversible P2Y12 inhibitor in humans

   
@article{APS10395,
	author = {Yuan-dong Zheng and Hua Zhang and Yan Zhan and Yi-cong Bian and Sheng Ma and Hai-xian Gan and Xiao-juan Lai and Yong-qiang Liu and Yan-chun Gong and Xue-fang Liu and Hong-bin Sun and Yong-guo Li and Da-fang Zhong and Li-yan Miao and Xing-xing Diao},
	title = {Pharmacokinetics, mass balance, and metabolism of [ 14 C]vicagrel, a novel irreversible P2Y12 inhibitor in humans},
	journal = {Acta Pharmacologica Sinica},
	volume = {42},
	number = {9},
	year = {2021},
	keywords = {},
	abstract = {Vicagrel, a novel irreversible P2Y12 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 [14C]vicagrel (120 μCi). Vicagrel absorption was fast (Tmax = 0.625 h), and the mean t1/2 of vicagrel-related components was ~38.0 h in both plasma and blood. The blood-to-plasma radioactivity AUCinf 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 AUC0–8 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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/10395}
}