Effects of food and gender on pharmacokinetics of ticagrelor and its main active metabolite AR-C124910XX in healthy Chinese subjects .

Abstract

The manuscript was mainly aimed to evaluate effects of food and gender on the pharmacokinetics of ticagrelor and its main active metabolite AR-C124910XX in healthy Chinese subjects observed in the bioequivalence studies of the two formulations of ticagrelor tablets. The single-dose, two-sequence, two-period and crossover studies were respectively conducted under fasting and fed conditions. Plasma samples were analyzed by an HPLC-MS/MS method. Log-transformed pharmacokinetic parameters of ticagrelor and AR-C124910XX obtained from the trials were compared by the mean of two one-sided t-test. Pharmacokinetic parameters of the two formulations were evaluated. The mean ticagrelor tmax value was delayed by 0.28-0.53 hours owing to meals. A 21.6-24.0% (p < 0.05) increase in the mean ticagrelor AUC* (body weight-normalized AUC) value was measured (fed vs. fasting). For AR-C124910XX, the mean T1/2 value was delayed by 0.84-1.33 hours (p < 0.05) due to meals. A 52.0-55.8% (p < 0.05) decrease in the mean Cmax* (body weight-normalized Cmax) value and a 15.6-16.9% (p < 0.05) decrease in the mean AUC* value were observed (fed vs. fasting). The female subjects exhibited higher exposures to ticagrelor and AR-C124910XX than the male subjects. Compared with other populations, the Chinese subjects in this study experienced a greater decrease in Cmax of AR-C124910XX due to meals. 21 adverse events of mild intensity occurred over the study periods. The studies showed food effects on the absorption of ticagrelor and the formation of AR-C124910XX, and gender effects on exposures to the drug after single oral-dose administration. .