| Indication | For the treatment of hypercholesterolemia. |
| Pharmacodynamics | Simvastatin, the methylated form of lovastatin, is an oral antilipemic agent which inhibits HMG-CoA reductase. simvastatin is used in the treatment of primary hypercholesterolemia and is effective in reducing total and LDL-cholesterol as well as plasma triglycerides and apolipoprotein B. |
| Mechanism of action | The 6-membered lactone ring of simvastatin is hydrolyzed in vivo to generate the beta,delta-dihydroxy acid, an active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme. Interference with the activity of this enzyme reduces the quantity of mevalonic acid, a precursor of cholesterol. |
| Absorption | Absorption of simvastatin, estimated relative to an intravenous reference dose, in each of two animal species tested, averaged about 85% of an oral dose. In animal studies, after oral dosing, simvastatin achieved substantially higher concentrations in the liver than in non-target tissues. |
| Volume of distribution | Not Available |
| Protein binding | Both simvastatin and its b-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. |
| Metabolism | Hepatic, simvastatin is a substrate for CYP3A4. |
| Route of elimination | Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces. |
| Half life | 3 hours |
| Clearance | Not Available |
| Toxicity | Not Available |