Lack of significant food effect on the pharmacokinetics of ticagrelor in healthy volunteers

What is known and Objective: Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist and has been approved in the European Union and the USA for the reduction of clinical thrombotic events in patients with acute coronary syndromes. This study aimed to assess the effect of food on ticagrelor pharmacokinetics. Methods: The study was an open-label, randomized, 2-period crossover single-centre trial; 26 healthy volunteers received a single 270 mg (3 x 90 mg tablets) ticagrelor dose orally following: (i) a 10-h overnight fast; and (ii) after a standard high-fat, high-calorie breakfast. Ticagrelor and AR-C124910XX (a major pharmacologically active metabolite) plasma concentrations were quantified for pharmacokinetic analysis. Results: Ticagrelor median time to maximum concentration (tmax; 2.5 h vs. 1.5 h) was slightly delayed in the fed vs. fasting state. Maximum concentration of ticagrelor (Cmax) was comparable between the two states with 95% confidence intervals (CI) of the geometric least-squares (GLS) mean ratio (0.851.03) being within no-effect limits (0.801.25). Ticagrelor exposure was slightly higher with food intake; area under the plasma concentrationtime curve from zero to infinity (AUC) was 21% higher compared with fasting state (95% CI of GLS mean ratio = 1.131.30). For AR-C124910XX, AUC (95% CI of GLS mean ratio = 0.931.07) was unaffected by food consumption. Median tmax of the metabolite was slightly longer in the fed than fasting state (3.5 h vs. 1.5 h). Mean Cmax for AR-C124910XX was slightly lower (22%) with food intake vs. fasting (95% CI of GLS mean ratio 0.690.88). What is new and Conclusion: Food effects on ticagrelor AUC and AR-C124910XX Cmax were small and are considered to be of minimal clinical significance. Thus, ticagrelor can be administered with or without food.