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

作　　者：Yi-min CUI Zi-ning WANG Xiao-wen CHEN Hui-lin ZHANG Xia ZHAO Ying ZHOU 

机构地区：[1]Department of Pharmacy,Base for Clinical Trial,Peking University First Hospital,Beijing 100034,China [2]Lilly Suzhou Pharmaceutical Co,Ltd,Shanghai 200021,China

出　　处：《Acta Pharmacologica Sinica》2012年第11期1395-1400,共6页中国药理学报（英文版）

摘　　要：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.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.

关 键 词：PRASUGREL platelet aggregation PHARMACOKINETICS PHARMACODYNAMICS dose regimen healthy Chinese subject 

分 类 号：S859.796[农业科学—临床兽医学] TE626.32[农业科学—兽医学]