Bioequivalence and Pharmacokinetic Profiles of 2 Trimetazidine Modified-release Tablets Under Fasting and Fed Conditions in Chinese Healthy Subjects.

ABSTRACT

This study aims to assess the bioequivalence of test and reference formulations of trimetazidine dihydrochloride in healthy Chinese volunteers under fasting and fed conditions, and to determine the effect of food on the pharmacokinetic profiles of both formulations. A randomized, open-label, crossover, four-period study with a 7-day washout period was conducted in 24 healthy Chinese subjects. The subjects fasted for at least 10 hours before being given a single 35-mg dose of the test and reference tablets. Venous blood samples were taken from predose at 0 hours to postdose at 36 hours at scheduled time points. The main pharmacokinetic parameters were calculated with a noncompartmental model. The nonparametric test of Tmax under both conditions showed no significant difference between the two formulations (P > .05). The 90% confidence intervals of geometric mean ratio of lnCmax and lnAUC0→∞ (the logarithmic values of area under the plasma concentration-time curve [AUC] and mean maximum plasma concentration [Cmax ]) all fell within 80%-125%. Cmax in the fed state was slightly higher than that in the fasting state (P < .05), while other pharmacokinetic parameters were comparable. No severe adverse events occurred. The test and reference formulations were bioequivalent under both fasting and fed conditions. Food did not affect the pharmacokinetic profiles of trimetazidine in Chinese healthy volunteers, therefore trimetazidine is suitable for administration under fasting or fed conditions.