Forcad Mechanism of Action

HMG-CoA Reductase Inhibitor.
Pharmacology: Simvastatin is a hypolipidaemic agent; it is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate-determining enzyme for cholesterol synthesis. HMG-CoA reductase inhibitors (sometimes called "statins") reduce total cholesterol, low-density lipoprotein (LDL)-cholesterol, and very-low-density lipoprotein (VLDL)-cholesterol concentrations in plasma. They also tend to reduce triglyceride and to increase high-density lipoprotein (HDL)-cholesterol concentrations. They are considered to exert their hypocholesterolaemic action by stimulating an increase in LDL-receptors on hepatocyte membranes thereby increasing the clearance of LDL from the circulation.
Pharmacokinetics: Simvastatin is absorbed from the gastrointestinal tract and is hydrolyzed to its active β-hydroxyacid form. Other active metabolites have been detected and a number of inactive metabolites are also formed. Simvastatin undergoes extensive first pass metabolism in the liver, its primary site of action. Less than 5% of the oral dose has been reported to reach the circulation as active metabolites. Both simvastatin and its β-hydroxyacid metabolites are about 95% bound to plasma proteins. It is mainly excreted in the feces via the bile as metabolites. About 10% to 15% is recovered in the urine, mainly in inactive forms. The half-life of the active metabolites is 1.9 hours.