Comparative Steady State Cross-Over Bioequivalence Study of 35mg Trimetazidine Extended-Release Tablets

Abstract

Background: Trimetazidine (TMZ), an anti-ischemic drug, protects the myocardial cell from the harmful effects of ischemia. This study is aimed to determine bioequivalence between the test (Trimetazidine ER Tablet of Cipla Limited, India) and the reference (Preductal MR Tablet of Servier, France) products at steady state in 24 healthy adult male volunteers under fed conditions. Method: We conducted a randomized, open-label, balance, two-treatment, two-period, two-sequence, crossover steady state bioequivalence study separated by a washout period of 7 days. Participants were randomly assigned to receive 35mg of trimetazidine either test or reference products twice daily (12 hours interval) after standardized breakfast and dinner on day 1 to day 4, followed by single dose on day 5 after breakfast in each study period. Post-dose blood samples were collected up to 36 hours and analyzed for trimetazidine using a validated LC-MS/MS method. Steady-state trimetazidine concentrations were statistically analyzed using SAS ® software for windows (version 9.1). Results: The 90% confidence intervals (CI) for trimetazidine (AUC Tau , and C maxss) were the conventional bioequivalence range of 80.00-125.00%, thus permitting one to conclude for bioequivalence. Furthermore, both formulations were well tolerated and had no-serious adverse event reported. Conclusion: The test and reference formulations of trimetazidine meet the regulatory criteria for bioequivalence both in terms of rate and extent of absorption.