Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects

• Published in: Acta pharmacologica Sinica Vol. 33; no. 11; pp. 1395 - 1400
• Main Authors: Cui, Yi-min, Wang, Zi-ning, Chen, Xiao-wen, Zhang, Hui-lin, Zhao, Xia, Zhou, Ying
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.11.2012
• Subjects: Adult; Area Under Curve; Asian Continental Ancestry Group; China; Chromatography, Liquid; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Original; Piperazines - administration & dosage; Piperazines - pharmacokinetics; Piperazines - pharmacology; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - pharmacokinetics; Platelet Aggregation Inhibitors - pharmacology; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists - administration & dosage; Purinergic P2Y Receptor Antagonists - pharmacokinetics; Purinergic P2Y Receptor Antagonists - pharmacology; Tandem Mass Spectrometry; Thiophenes - administration & dosage; Thiophenes - pharmacokinetics; Thiophenes - pharmacology; 中国; 健康; 加剂量; 活性代谢产物; 活性代谢物; 药代动力学; 药效学; 血小板聚集; China
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2012.120

Aim： To characterize the pharmacokinetics （PKs）, pharmacodynamics （PDs）, and tolerability of different dose regimens of prasugrel in healthy Chinese subjects. Methods： This was a single-centered, open-label, parallel-design study. Subjects received a single loading dose （LD） of prasugrel followed by once-daily maintenance dose （MD） for 10 d. They were enrolled into 3 groups： 60 mg LD/IO mg MD; 30 mg LD/7.5 mg MD; 30 mg LD/5 mg MD. Blood samples were collected after the first and last dose. The serum concentration of the active metabolite of prasugrel was determined using a LC/MS/MS method. Platelet aggregation was assessed using the VerifyNow-P2Y12 assay. Results： Thirty-six healthy native Chinese subjects （19 males） aged 18-45 were enrolled; mean age and body weight were similar across the treatment groups （n=12 for each）. The metabolite AUC0-4 and Cmax increased dose-proportionally across the dose range of 5 mg to 60 mg. The median Tmax was 0.5 h in all groups. The PD parameters, indicated by the inhibition of ADP-induced platelet aggregation, were met more rapidly in the 60 mg group than the 30 mg group after the LD （94%-98%）. This high degree of inhibition of platelet aggregation was maintained following the 10 mg MD （87%-90%） and was lower in the 7.5 mg and 5 mg MD groups （79%-83% and 64%-67%, respectively）. Prasugrel was well tolerated in healthy Chinese subjects for single doses up to 60 mg and a MD of 10 mg for 10 d. Conclusion： The PKs and PDs of the active metabolite of prasugrel were similar to those in Chinese subjects reported by a previous bridging study, which demonstrated that the exposure to the active metabolite in Chinese subjects was higher than in Caucasians.