SandboxAlonso
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]
For patient information about Simvastatin, click here.
Synonyms / Brand Names: ZOCOR®,generic
Overview
Simvastatin (INN) (Template:PronEng) is a hypolipidemic drug belonging to the class of pharmaceuticals called "statins". It is used to control hypercholesterolemia (elevated cholesterol levels) and to preventcardiovascular disease. Simvastatin is a synthetic derivate of a fermentation product of Aspergillus terreus.
History
The development of simvastatin was closely linked with the research and development of lovastatin. Biochemist Jesse Huff and his colleagues atMerck began researching the biosynthesis of cholesterol in the early 1950s. In 1956, mevalonic acid was isolated from a yeast extract by Karl Folkers, Carl Hoffman, and others at Merck; while Huff and his associates confirmed that mevalonic acid was an intermediate in cholesterol biosynthesis. In 1959, the HMG-CoA reductase enzyme (a major contributor of internal cholesterol production) was discovered by researchers at the Max Planck Institute. This discovery encouraged scientists worldwide to find an effective inhibitor of this enzyme.
By 1976, Akira Endo had isolated the first inhibitor (compactin ML-236B) from the fungus, Penicillium citrinium in Sankyo, Japan.[1] In 1979, Hoffman and colleagues isolated lovastatin from a strain of the fungus Aspergillus terreus. While developing and researching lovastatin, Merck scientists synthetically derived a more potent HMG-CoA reductase inhibitor from a fermentation product of Aspergillus terreus, which was designated MK-733 (later to be named simvastatin).[2]
Category
Alcohols,Carboxylate esters,Lactones,Merck,Statins,Tetrahydropyrans,World Health Organization essential medicines,Neuroprotective agents,Cardiovascular Drugs
FDA Package Insert
Indications and Usage | Dosage and Administration | Dosage Forms and Strengths | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Use in Specific Populations | Overdosage | Description | Clinical Pharmacology | Nonclinical Toxicology | Clinical Studies | How Supplied/Storage and Handling | Patient Counseling Information | Labels and Packages
Mechanism of Action
Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, simvastatin reduces VLDL and TG and increases HDL-C.
Interaction with Alcohol
The drug should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease.
References
- ↑ Liao and Laufs. Pleiotropic Effects of Statins.(2005) Annu. Rev. Pharmacol. Toxicol:45:89-118
- ↑ Olivia Williams, Anne-Marie Jacks, Jim Davis, Sabrina Martinez (1998). "Case 10: Merck(A): Mevacor*". In Ed. Allan Afuah. Innovation Management - Strategies, Implementation, and Profits. Oxford University Press.