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Pharmacokinetics, mass balance, and metabolism of [14C]vicagrel, a novel irreversible P2Y12 inhibitor in humans.
Zheng, Yuan-Dong; Zhang, Hua; Zhan, Yan; Bian, Yi-Cong; Ma, Sheng; Gan, Hai-Xian; Lai, Xiao-Juan; Liu, Yong-Qiang; Gong, Yan-Chun; Liu, Xue-Fang; Sun, Hong-Bin; Li, Yong-Guo; Zhong, Da-Fang; Miao, Li-Yan; Diao, Xing-Xing.
Affiliation
  • Zheng YD; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201210, China.
  • Zhang H; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Zhan Y; Department of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, 215123, China.
  • Bian YC; Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University, Suzhou, 215006, China.
  • Ma S; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201210, China.
  • Gan HX; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Lai XJ; Department of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, 215123, China.
  • Liu YQ; Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University, Suzhou, 215006, China.
  • Gong YC; Department of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, 215123, China.
  • Liu XF; Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University, Suzhou, 215006, China.
  • Sun HB; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201210, China.
  • Li YG; Jiangsu Vcare PharmaTech Co. Ltd., Nanjing, 211800, China.
  • Zhong DF; Jiangsu Vcare PharmaTech Co. Ltd., Nanjing, 211800, China.
  • Miao LY; Jiangsu Vcare PharmaTech Co. Ltd., Nanjing, 211800, China.
  • Diao XX; Jiangsu Vcare PharmaTech Co. Ltd., Nanjing, 211800, China.
Acta Pharmacol Sin ; 42(9): 1535-1546, 2021 Sep.
Article in En | MEDLINE | ID: mdl-33244163
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phenylacetates / Thiophenes / Purinergic P2Y Receptor Antagonists Limits: Adult / Humans / Male Language: En Journal: Acta Pharmacol Sin Journal subject: FARMACOLOGIA Year: 2021 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phenylacetates / Thiophenes / Purinergic P2Y Receptor Antagonists Limits: Adult / Humans / Male Language: En Journal: Acta Pharmacol Sin Journal subject: FARMACOLOGIA Year: 2021 Document type: Article Affiliation country: Country of publication: