Pharmacokinetics, bioequivalence and safety of two formulations of ticagrelor in healthy Chinese subjects: Effects of food

Abstract

Ticagrelor is the first reversible ADP P2Y12 receptor antagonist approved to treat acute coronary syndrome. To investigate the effects of food on the pharmacokinetics (PK), bioequivalence and safety of ticagrelor tablets in healthy Chinese volunteers, 32 healthy subjects were randomly assigned to an open-labelled, single-centre, two-preparation, two-sequence, two-cycle, double-crossover trial under fasting and fed conditions, with a washout period of 7 days. Plasma concentrations of ticagrelor and AR-C124910XX were determined using LC-MS/MS. The C_max , AUC_0-t and AUC_0-∞ of the reference and test tablets were determined using ANOVA and the USFDA bioequivalence statistical criterion of 90% CI for the 80%-125% range (p ≤ 0.05) of the geometric mean ratios. Adverse events (AEs) were observed and recorded. Food consumption increased the AUC_0-t and AUC_0-∞ (p < 0.01) of ticagrelor, lowered the C_max (p < 0.01) and prolonged the t_12z (p < 0.05) of AR-C124910XX. The effects of food on the reference preparations were comparable. Formulation, time and sequence had no significant effects on the PK parameters (p ≧ 0.05). The test formulation was bioequivalent to the reference formulation as the geometric mean ratios under fasting and fed conditions were within equivalence limits (80%-125%). No serious AEs were reported. Thus, test and reference ticagrelor are bioequivalent in Chinese subjects under fasting and fed conditions.

Keywords: bioequivalence; food; pharmacokinetics; safety; ticagrelor.