Carvidon/Carvidon-MR Mechanism of Action

Antianginal and anti-ischaemic.
Pharmacology: Carvidon: Trimetazidine belongs to a new class of compounds that display anti-ischaemic effects without inducing haemodynamic changes and improves the status of the ischaemic myocardium. It exerts its antianginal effects through a direct cytoprotective action on the myocardium, thereby, avoiding the side effects of impaired left ventricular function, excessive peripheral vasodilation and other disadvantages associated with the use of comparative antianginal agents.
Carvidon-MR: Mechanism of Action: There are several possible mechanisms of action by which trimetazidine promotes preservation of membrane structures and cellular function, thereby allowing the ischaemic myocardial cell to more rapidly restore its energy reserves. The main mechanisms are: Limitation of intracellular acidosis; improvement in transmembrane ion exchanges and calcium overload; prevention of excessive free radical production; inhibition of the inflammatory reaction and preservation of mitochondrial function.
Pharmacokinetics: Trimetazidine is >95% non-ionized at physiological pH, permitting the drug to pass through lipoprotein membranes. It is rapidly and completely absorbed from the gastrointestinal tract after oral ingestion. C_max is 1.8 hrs and plasma half-life is 6 hrs. Plasma protein-binding is low and the volume of distribution is 320 L. Four pathways of metabolism are known but metabolism is not extensive, with 51% of unchanged drug eliminated in urine. Elimination is rapid (t_½=6 hrs) and predominantly renal. Sixty percent of the drug is excreted unchanged in the urine. Food intake does not interfere with the pharmacokinetics of trimetazidine.