TMZ-MR

TMZ-MR Mechanism of Action

trimetazidine

Manufacturer:

Sydler Remedies

Distributor:

Bell-Kenz Pharma
Full Prescribing Info
Action
Pharmacology: Pharmacodynamics: Trimetazidine is a unique anti-ischaemic drug, which protects the myocardial cell from the harmful effects of ischaemia. The mode of action is Trimetazidine is different from beta-blockers, calcium channel blockers and nitrates. Unlike these antianginal agents, which affect haemodynamic determinants of myocardial oxygen supply-demand balance, Trimetazidine prevents the damage to the myocardial cell during an ischaemic episode. Trimetazidine inhibits fatty acid oxidation secondary to an inhibition of long-chain 3-ketoacyl CoA thiolase (KAT), resulting in an increase in glucose oxidation. This results in switching energy substrate preference from fatty acid oxidation to the more efficient glucose oxidation which explains the antianginal properties.
Trimetazidine prevents intracellular metabolic changes such as depletion of adenosine triphosphate (ATP) and phosphocreatinine, accumulation of protons, and toxic free radical generation which result from ischaemia and reperfusion in the myocardium. Trimetazidine exerts protective effects against ionic disturbance due to ischemia-reperfusion in fatty acid-perfused hearts, but depending on the degree of severity. Trimetazidine has also been proven to provide membrane protection through a large increase in phospholipids turnover. This effect contributes to a reorganization of fatty acid utilization balance, resulting in their decreased availability for energy production. As such, Trimetazidine raises cell tolerance to ischaemia-reperfusion injury. Trimetazidine enhances the metabolic status of cardiomyocytes in hypoperfused regions in patients with previous myocardial infarction as well as those with a history of angina.
Pharmacokinetics: Trimetazidine is absorbed through the intestinal mucosa with a Tmax (time to reach maximum concentration) of 5.4 hours. The Cmax is 89 microg/L. The t75 (time during which the plasma concentration remains above 75% of Cmax) is 11 hours. The bioavailability is 87%, slightly inferior with Trimetazidine modified release than with the immediate-release formulation, explaining the increase in the dose of Trimetazidine (35 mg compared with 20 mg for the immediate-release tablet). The bioavailability is not influenced by food. The steady state is reached 2 to 3 days after starting the treatment. The volume of distribution, unaffected by the modified-release formulation, is 4.8 L/kg which means good tissue diffusion. Protein binding affinity is low (16%), with equal binding to albumin and alpha-glycoprotein. No uptake of Trimetazidine in red blood cells was observed. The major drug related component observed in plasma and urine was unchanged Trimetazidine. Trimetazidine and its metabolites are predominantly eliminated in urine. A small proportion of Trimetazidine is excreted in the faeces (about 6% of the administered dose). The renal Trimetazidine clearance is 350 mL/min and is independent of the urine and plasma concentration of the drug, whereas it is correlated with renal creatinine clearance. That is why the elimination half-life is shorter in the healthy patient compared with the elderly patient (7 and 12 hours, respectively). Trimetazidine can be safely prescribed without adapting the dose in elderly patients and in case of renal insufficiency (if creatinine clearance remains above 15 mL/min).
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in