RiteMED Trimetazidine Mechanism of Action

Pharmacology: Pharmacodynamics: Findings from in vitro and ex vivo studies have demonstrated that trimetazidine is beneficial for ischemia and heart failure by (1) improving metabolic efficiency by changing the source of ATP production to glucose oxidation which decreases the consequences of recurrent ischemia and enhances left ventricular performance, (2) protecting endothelial function by increasing endothelial nitric synthase activity and nitric oxide availability, (3) preserving mitochondrial function and energy metabolism thus reducing ischemic left ventricular dysfunction, (4) limiting intracellular acidosis, (5) limiting sodium and calcium accumulation, and (6) inhibiting neutrophil infiltration.
Pharmacokinetics: Trimetazidine is rapidly absorbed from the intestinal mucosa after oral administration. In 13 healthy volunteers, the mean peak plasma trimetazidine concentration (C_max; 53.6 mcg/L) was reached 1.8 hours after a single 20 mg (immediate release) oral dose. After twice daily administration of trimetazidine 20 mg for 15 days, C_max (84.8 mcg/L) was reached in 1.7 hours. The area under the plasma trimetazidine concentration-time curve (AUC_0-∞) was 508.9 mcg·h/L after a single 20 mg dose and 831.4 mcg·h/L after repeated administration. Steady state levels were reached within 24 hours and remained stable for the study duration.
Trimetazidine is only weakly protein bound in plasma (~16%) and therefore is widely distributed throughout the body. In 11 healthy volunteers, the volume of distribution (Vd) of trimetazidine was 318.6 L after a 40 mg intravenous dose.
The elimination half-life of trimetazidine 20 mg is about 6 hours after single or repeated oral administration. More than 80% of an administered dose of trimetazidine is excreted in urine within 48 hours, with 62% of the drug eliminated unchanged. Eight metabolites have been detected in urine, however, little is known of their properties.
Comparative Bioavailability Study: Trimetazidine (Vestar) 35 mg Modified-release Tablet (manufactured by Amherst, Philippines): Trimetazidine (Vestar) 35 mg modified-release tablet was shown to have comparable bioavailability to the reference product (innovator) in adults under fasting conditions. After multiple oral administration of trimetazidine (Vestar) 35 mg modified-release tablet, mean peak trimetazidine plasma concentration (C_max) at steady state (8th dosing interval) of 0.1 ± 0.01 mcg/mL was achieved within 4.78 ± 1.52 hours (T_max). The area under the plasma concentration time-curve (AUC_0-24h) at steady state was 1.07 ± 0.24 mcg·h/mL.