Bioequivalence study of two formulations of 35mg trimetazidine modified release tablets in healthy thai volunteers under fasting and fed conditions

Abstract

Background: The generic product of trimetazidine, an anti-anginal agent, is currently available in Thailand. Bioequivalence study is used to compare rate and extent of absorption between generic and innovator's products. Objective: To determine the bioavailability of two modified release tablets of 35mg trimetazidine dihydrochloride (Matenol® MR; generic product and Vastarel® MR; innovator's product) Materials and methods: The study was conducted according to a single-dose, two-treatment, two-period, two sequence randomized crossover design under fasting and fed conditions with a minimum of 7 days washout period. Twenty-four healthy Thai male and female volunteers were enrolled; however, only twenty-two subjects in the fasting group and twenty-three subjects in the fed group were completed the studies. For both conditions, each volunteer received a 35mg trimetazidine modified release tablet of both formulations. Every volunteers were obtained blood samples 16 times over a period of 24 hours after each oral administration. The trimetazidine plasma concentrations were quantified using a validated method employing liquid chromatography with tandem mass spectrometry with the lower limit of quantification of 0.25 ng/mL. All of the pharmacokinetic parameters were investigated using noncompartmental analysis model. Results: The 90% confidence interval of the geometric mean ratio of C max , AUC 0-t and AUC 0-∞ were within the equivalence criteria (80.00-125.00%) which were 105.53% (95.71%-116.36%), 104.28% (96.24%-112.98%, and 105.26% (96.61%-114.67%) under fasting condition and 110.21% (102.72%-118.25%), 101.95% (94.33%- 119.19%), and 99.7% (91.18%-109.02%) under fed condition, respectively. No statistical differences of median Tmax (p > 0.05) between two formulations in both conditions were observed. Furthermore, both preparations were well tolerated and had a few non-serious adverse events including nausea, dizziness, drowsiness and headache. Conclusion: These two trimetazidine products have comparable bioavailability. © 2011 Chandranipapongse W, et al.