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

• Published in: Basic & clinical pharmacology & toxicology Vol. 132; no. 4; pp. 313 - 320
• Main Authors: Dong, Chengmei, Zhang, Xiaonan, Zhang, Yalan, Ouyang, Wenjuan, Peng, Daizhuang, Li, Xiaomin, Li, Dai, Qin, Qun
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2023
• Subjects: Bioequivalence; Chromatography, Liquid; East Asian People; Fasting; Food; Food consumption; Healthy Volunteers; Humans; Pharmacokinetics; Pharmacology; Safety; Tablets; Tandem Mass Spectrometry; Therapeutic Equivalency; Ticagrelor; Variance analysis; pharmacokinetics; ticagrelor; safety; bioequivalence; food
• ISSN: 1742-7835; 1742-7843; 1742-7843
• DOI: 10.1111/bcpt.13830

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 Cmax, AUC0–t and AUC0–∞ 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 AUC0–t and AUC0–∞ (p < 0.01) of ticagrelor, lowered the Cmax (p < 0.01) and prolonged the t12z (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. Food consumption could effect the AUC of ticagrelor and the Cmax & t1/2z of AR‐C124910XX. No significant differences in the incidence of AEs between test and reference tablets. Ticagrelor was bioequivalent to the reference preparation during fasting and fed conditions.