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Pharmacokinetics, mass balance, and metabolism of [ 14 C]vicagrel, a novel irreversible P2Y 12 inhibitor in humans.
- Source :
-
Acta pharmacologica Sinica [Acta Pharmacol Sin] 2021 Sep; Vol. 42 (9), pp. 1535-1546. Date of Electronic Publication: 2020 Nov 26. - Publication Year :
- 2021
-
Abstract
- Vicagrel, a novel irreversible P2Y <subscript>12</subscript> 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 [ <superscript>14</superscript> C]vicagrel (120 µCi). Vicagrel absorption was fast (T <subscript>max</subscript> = 0.625 h), and the mean t <subscript>1/2</subscript> of vicagrel-related components was ~38.0 h in both plasma and blood. The blood-to-plasma radioactivity AUC <subscript>inf</subscript> 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 <subscript>0-8 h</subscript> 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.<br /> (© 2020. CPS and SIMM.)
- Subjects :
- Administration, Oral
Adult
Clopidogrel
Humans
Male
Phenylacetates blood
Phenylacetates chemistry
Purinergic P2Y Receptor Antagonists blood
Purinergic P2Y Receptor Antagonists chemistry
Thiophenes blood
Thiophenes chemistry
Phenylacetates metabolism
Phenylacetates pharmacokinetics
Purinergic P2Y Receptor Antagonists metabolism
Purinergic P2Y Receptor Antagonists pharmacokinetics
Thiophenes metabolism
Thiophenes pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1745-7254
- Volume :
- 42
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Acta pharmacologica Sinica
- Publication Type :
- Academic Journal
- Accession number :
- 33244163
- Full Text :
- https://doi.org/10.1038/s41401-020-00547-7