Effect of age and gender on pharmacokinetics and pharmacodynamics of a single ticagrelor dose in healthy individuals.

PURPOSE: The aim of this study was to assess age and gender effects on ticagrelor pharmacokinetics and pharmacodynamics (PK/PD).
METHODS: Forty healthy individuals [18-45 years (young); ≥ 65 years (elderly); ten men, ten women per age group) received 200 mg ticagrelor.
RESULTS: Ticagrelor was rapidly absorbed [time to maximum concentration (C(max)) (t(max)) 2.5-3.0 h], and its major active metabolite, AR-C124910XX rapidly formed (t(max) 3.0-3.5 h) in all groups. Ticagrelor exposure was higher in elderly vs. the young [area under the curve from time 0 to infinity (AUC(0-∞)) 52%; C(max) 63% higher] and women vs. men (AUC(0-∞) 37%; C(max) 52% higher). Mean terminal elimination half-life was slightly longer in women vs. men but was unaffected by age. Similar results were observed for AR-C124910XX (elderly vs. young, AUC(0-∞) 48%; C(max) 61% higher), and in women vs. men (AUC(0-∞) 55%; C(max) 56% higher). Across all groups, ticagrelor produced substantial final-extent inhibition of platelet aggregation (IPA): >90% at 4 and 8 h postdose. Individuals with highest ticagrelor exposure (i.e., elderly) had the lowest IPA, indicating an age-related platelet sensitivity effect. In young individuals, platelet sensitivity was greater in men vs. women. Ticagrelor tolerability was not affected by age or gender.
CONCLUSIONS: Systemic exposures to ticagrelor and AR-C124910XX were higher in elderly vs. young and in women vs. men. Age- and gender-related changes in IPA were apparent, but substantial IPA was achieved in all groups. No adjustment in ticagrelor dose should be considered necessary based on age and gender.