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

Article Details

Citation

Copy to clipboard

Zheng YD, Zhang H, Zhan Y, Bian YC, Ma S, Gan HX, Lai XJ, Liu YQ, Gong YC, Liu XF, Sun HB, Li YG, Zhong DF, Miao LY, Diao XX

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

Acta Pharmacol Sin. 2021 Sep;42(9):1535-1546. doi: 10.1038/s41401-020-00547-7. Epub 2020 Nov 26.

PubMed ID

33244163 [ View in PubMed

]

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 [(14)C]vicagrel (120 microCi). 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Vicagrel	P2Y purinoceptor 12	Protein	Humans	Unknown	Antagonist Inhibitor	Details