Angimed Mechanism of Action

Pharmacology: Pharmacodynamics: Finding from in vitro and ex vivo studies of myocardial ischemia have demonstrated that trimetazidine (1) limits intracellular acidosis, (2) limits sodium and calcium accumulation, (3) maintains intracellular ATP levels and reduces creatine phosphokinase release, (4) preserves mitochondrial function, (5) reduces myocardial fatty acid metabolism and increases myocardial glucose metabolism, (6) protects against oxygen free radical-induced membrane damage, and (7) inhibits neutrophil infiltration.
By inhibiting fatty acid metabolism and secondarily stimulating glucose metabolism, trimetazidine optimizes cardiac metabolism and thus protects the heart against the harmful effects of ischemia. However, the definitive mechanism of action of trimetazidine has yet to be determined.
Pharmacokinetics: Trimetazidine is rapidly absorbed from the intestinal mucosa after oral administration.
After multiple oral administration of a 35 mg MR tablet twice daily for four days to fasted normal adults, mean peak trimetazidine plasma concentration (C_max) at steady (8^th dosing interval of 0.1±0.01 μg/mL was achieved in 4.78 ± 1.52 hours (T_max). The area under the plasma concentration-time curve (AUC_0-∞) at steady state was 1.07 ± 0.24 μg·hr/mL. The elimination half-life was 9.75 ± 10.89 hours.
Trimetazidine is only weakly protein bound in plasma (~16%) and therefore is widely distributed throughout the body. In 11 healthy volunteers, the volume of distributed (V_d) of trimetazidine was 318.6 L after a 40 mg intravenous dose.
The elimination half-life of immediate release 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.
The Trimetazidine MR 35 mg twice daily regimen is likely to result in improved patient compliance and better patient anti-ischemic protection in the early morning.