title: Pharmacodynamics, pharmacokinetics and safety of ticagrelor in Asian patients with stable coronary artery disease.
abstract: This randomized, active-controlled, double-blind study assessed the pharmacodynamics, pharmacokinetics and safety of ticagrelor in Japanese patients and a smaller cohort of non-Japanese Asian patients. The study recruited patients aged 20-80 years who had received aspirin 75-100 mg/day for ≥2 weeks and had percutaneous coronary intervention or acute coronary syndrome >3 months previously. Patients received 4 weeks' treatment with ticagrelor 45 mg bid, ticagrelor 90 mg bid or clopidogrel 75 mg qd (all with aspirin). The inhibition of platelet aggregation (IPA, final-extent) and pharmacokinetics of ticagrelor were assessed on days 1 and 28. Overall, 139 Asian patients were randomized (ticagrelor 45 mg bid, n = 50; ticagrelor 90 mg bid, n = 43; clopidogrel, n = 46) of whom 118 were Japanese. Mean final-extent IPA was greater with ticagrelor 90 mg bid versus ticagrelor 45 mg bid and with both ticagrelor doses versus clopidogrel. At the end of the dosing interval on day 28, mean final-extent IPA was 10.0% higher (95% confidence interval 0.5-19.5%) for ticagrelor 90 mg bid versus ticagrelor 45 mg bid, 15.1% higher (5.8-24.4%) for ticagrelor 45 mg bid versus clopidogrel, and 25.1% higher (15.5-34.7%) for ticagrelor 90 mg bid versus clopidogrel. In Japanese patients, exposure to ticagrelor and its active metabolite AR-C124910XX increased dose-proportionally. The safety profile of ticagrelor was consistent with previous studies. Ticagrelor was associated with enhanced IPA versus clopidogrel in Japanese patients.
authors.affiliation: Department of Cardiology, Tokushima Red Cross Hospital, Tokushima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hiasa
authors.forename: R
authors.initials: R
authors.lastname: Teng
authors.forename: H
authors.initials: H
authors.lastname: Emanuelsson
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D010979:Platelet Function Tests; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult
chemical_list: C561701:AR C124910XX; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin