|Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects|
|Cui, Yi-min1; Wang, Zi-ning1; Chen, Xiao-wen2; Zhang, Hui-lin1; Zhao, Xia1; Zhou, Ying1|
|关键词||prasugrel platelet aggregation pharmacokinetics pharmacodynamics dose regimen healthy Chinese subject|
|刊名||ACTA PHARMACOLOGICA SINICA|
|WOS标题词||Science & Technology|
|类目[WOS]||Chemistry, Multidisciplinary ; Pharmacology & Pharmacy|
|研究领域[WOS]||Chemistry ; Pharmacology & Pharmacy|
|关键词[WOS]||P2Y(12) RECEPTOR ANTAGONIST ; ACUTE CORONARY SYNDROMES ; ANTIPLATELET AGENT ; CLOPIDOGREL ; PHARMACOLOGY|
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/10 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-P2Y(12) 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 AUC(0-4) and C-max increased dose-proportionally across the dose range of 5 mg to 60 mg. The median T-max 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.
|资助机构||Eli Lilly and Company, Indianapolis, Indiana, USA|
|作者单位||1.Peking Univ, Hosp 1, Dept Pharm, Base Clin Trial, Beijing 100034, Peoples R China|
2.Lilly Suzhou Pharmaceut Co Ltd, Shanghai 200021, Peoples R China
|Cui, Yi-min,Wang, Zi-ning,Chen, Xiao-wen,et al. Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects[J]. ACTA PHARMACOLOGICA SINICA,2012,33(11):1395-1400.|
|APA||Cui, Yi-min,Wang, Zi-ning,Chen, Xiao-wen,Zhang, Hui-lin,Zhao, Xia,&Zhou, Ying.(2012).Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects.ACTA PHARMACOLOGICA SINICA,33(11),1395-1400.|
|MLA||Cui, Yi-min,et al."Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects".ACTA PHARMACOLOGICA SINICA 33.11(2012):1395-1400.|