title: Pharmacokinetics, pharmacodynamics, and tolerability of single and multiple doses of ticagrelor in Japanese and Caucasian volunteers.
abstract: OBJECTIVE
  Two studies assessing ticagrelor pharmacokinetics, pharmacodynamics, and tolerability in healthy Japanese and Caucasian volunteers.
  
  
  METHODS
  Single-ascending dose (SAD) study: Japanese (n = 20) and Caucasians (n = 20) received single doses of ticagrelor (50, 100, 200, 300, 400, and 600 mg) or placebo. Multiple-ascending dose (MAD) study: Japanese (n = 36) and Caucasians (n = 36) received single doses of 100 mg or 300 mg ticagrelor (day 1), twice-daily 100 mg or 300 mg ticagrelor, or placebo (days 4 â 9), and single doses of 100 mg or 300 mg ticagrelor (day 10).
  
  
  RESULTS
  Exposure to ticagrelor and its active metabolite, AR-C124910XX, was generally higher in Japanese vs. Caucasians. In the SAD study, area under the plasma concentration-time curve (AUC) values were 33% (ticagrelor) and 55% (AR-C124910XX) greater in Japanese vs. Caucasians following 600 mg ticagrelor. In the MAD study, AUC values of ticagrelor and AR-C124910XX following multiple doses of ticagrelor 100 mg and 300 mg were statistically significantly greater (33 - 48%) in Japanese vs. Caucasians. In both groups, mean peak inhibition of platelet aggregation was > 86% after single doses (>= 100 mg ticagrelor) and > 84% after multiple doses. Bleeding times were >= 60 minutes in more Japanese than Caucasians with multiple dosing of 100 mg and 300 mg ticagrelor Adverse events were similar between groups (mild-to-moderate intensity).
  
  
  CONCLUSIONS
  The pharmacokinetics and tolerability of ticagrelor were broadly similar in Japanese and Caucasians, although exposure was slightly greater in Japanese volunteers. Ticagrelor was generally well tolerated.
authors.forename: Renli
authors.initials: R
authors.lastname: Teng
authors.forename: Kathleen
authors.initials: K
authors.lastname: Butler
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D001711:Biotransformation; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D010979:Platelet Function Tests; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000077486:Ticagrelor; D014481:United States; D044465:White People; D055815:Young Adult
chemical_list: C561701:AR C124910XX; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine