China Greatvista Chemicals

Simvastatin

Simvastatin is a cholesterol-lowering medicine. It inhibits the production of cholesterol by the liver. It lowers overall blood cholesterol as well as blood LDL cholesterol levels. LDL cholesterol is believed to be the "bad" cholesterol that is primarily responsible for the development of coronary artery disease. Lowering LDL cholesterol levels retards progression and may even reverse coronary artery disease. Simvastatin is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol.

Simvastatin is a lipid-lowering agent that is derived synthetically from a fermentation product of Aspergillus terreus. After oral ingestion, simvastatin, which is an inactive lactone, is hydrolyzed to the corresponding -hydroxyacid form. This is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin is butanoic acid, 2,2-dimethyl-, 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[ 2-( tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1S-[ 1 ,3 ,7 ,8 (2S * ,4S * ),-8a ]]. The empirical formula of simvastatin is C25 H38 O5 and its molecular weight is 418.57.

Simvastatin is a hypocholesterolemic agent that acts as a potent inhibitor of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase. The inhibition of cholesterol biosynthesis causes a compensatory increase in the number of hepatic low-density lipoprotein (LDL) receptors, which results in greater uptake of LDL cholesterol particles from the blood. The most common clinical adverse effects observed with simvastatin are headache and mild gastrointestinal upset. Discontinuance of therapy because of myopathy is extremely rare (0.08%).1 On the other hand, lovastatin, another HMG-CoA reductase inhibitor that is structurally similar to simvastatin, has been associated with myopathy and rhabdomyolysis in patients receiving cyclosporine2,3 or when given in combination with gemfibrozil or niacin.4 We report a case of severe myopathy and rhabdomyolysis associated with concomitant use of simvastatin and gemfibrozil.