Evaluation of the pharmacokinetics, bioequivalence, and safety of two preparations of 20 mg trimetazidine

Abstract

Purpose: Trimetazidine (TMZ) is effective for the treatment of angina. Herein, we assessed the pharmacokinetics, safety, and bioequivalence of TMZ hydrochloride tablets from two different manufacturers in healthy Chinese individuals under both fasting and fed conditions. Methods: Twenty-eight participants were randomly assigned to either the fasting or fed arm in the single-center, randomized, open-label, crossover trial with a two-period, two-sequence design. TMZ levels in plasma were determined using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined using a non-atrioventricular model. Results: The mean AUC0-t, AUC0-∞, and Cmax for the test and reference formulations were 461.1 and 488.6 h·ng/mL, 471.3 and 500.2 h·ng/mL, and 50.0 and 52.6 ng/mL in the fasting arm, respectively. Similarly, in the fed arm, the values were 439.6 and 453.8 h·ng/mL, 448.4 and 462.9 h·ng/mL, and 64.0 and 66.8 ng/mL. The bioequivalence of both fasting and fed states for all parameters fell within the acceptable limits in both TMZ preparations. All recorded adverse events were mild. Conclusion: Overall, the test TMZ formulation was bioequivalent to the reference formulation and was safe for healthy Chinese subjects in both fasting and fed states.