Ticagrelor exposure was 33-48% greater in healthy Japanese versus Caucasian volunteers following multiple doses, but peak inhibition of platelet aggregation was >84% in both groups.
RCT (n=112)
Does ticagrelor exhibit different pharmacokinetics, pharmacodynamics, and tolerability in healthy Japanese compared to Caucasian volunteers?
Ticagrelor exposure is slightly higher in Japanese compared to Caucasian volunteers, though pharmacodynamics and tolerability remain broadly similar.
OBJECTIVES: Two studies assessing ticagrelor pharmacokinetics, pharmacodynamics, and tolerability in healthy Japanese and Caucasian volunteers. MATERIALS AND 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.
Teng et al. (Tue,) conducted a rct in Healthy volunteers (n=112). Ticagrelor vs. Placebo was evaluated on Pharmacokinetics, pharmacodynamics, and tolerability. Ticagrelor exposure was 33-48% greater in healthy Japanese versus Caucasian volunteers following multiple doses, but peak inhibition of platelet aggregation was >84% in both groups.