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

Trimetazidine dihydrochloride is a clinically effective, well tolerated anti-anginal agent which has been used in the prophylaxis and treatment of angina pectoris [1]. It also has been reported to be an effective agent for treating heart failure [2].The chemical structure of trimetazidine (TMZ) was shown in Figure 1. This drug acts via metabolic pathway by inhibition of the enzyme 3-ketoacyl coenzyme A thiolase, which results in a shift of cardiac metabolism from free fatty acid metabolism to glucose oxidation [3,4]. The cardiac utilization of glucose as a substrate for energy production is an effective approach to treat ischemic myocardium because it requires less oxygen consumption to produce the same amount of adenosine triphosphate [4,5]. Two formulations of trimetazidine are available in the clinical practice, the immediate-release and the modified-release tablet. The latter dosage form was developed to reduce frequency of dosing while maintaining sustained 24 hour coverage [6]. It has been shown to improve patient compliance thus more effective than a conventional tablet [7]. The pharmacokinetic profiles of two dosage forms of trimetazidine are different. After oral administration, both trimetazidine tablets are rapidly absorbed. The immediate-release tablet reached peak plasma concentration within 2 hours compared with 5 hours for the modified release tablet [8]. Trimetazidine is widely distributed throughout the body and mainly excreted in urine with approximately 60% eliminated unchanged. Eight metabolites of the drug have been detected in urine, but their properties were not known [1]. The elimination half-life of conventional tablet and modified-release tablet are approximately 6 and 7 hours, respectively [8].