title: Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Base for Clinical Trial, Peking University First Hospital, Beijing, China. cuiymzy@126.com
authors.forename: Yi-min
authors.initials: YM
authors.lastname: Cui
authors.forename: Zi-ning
authors.initials: ZN
authors.lastname: Wang
authors.forename: Xiao-wen
authors.initials: XW
authors.lastname: Chen
authors.forename: Hui-lin
authors.initials: HL
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D002681:China; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D053719:Tandem Mass Spectrometry; D013876:Thiophenes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride