What is Simvastatin? - By: William Rogdes

Simvastatin (INN) , (marketed under the brand names Zocor, Simvastatin, Simlup, Simcard and others) is a hypolipidemic drug within a class of pharmaceuticals referred to as "statins". It is used to manage hypercholesterolemia (elevated cholesterol levels) and to protect patients from incurring cardiovascular disease. Simvastatin is a synthetic derivate of Aspergillus terreus, a fermentation product.

History

The creation of simvastatin was closely connected with the research and development of Mevacor. Biochemist Jesse Huff and his colleagues at Merck began developing the biosynthesis of cholesterol in the early 1950s. In 1956, mevalonic acid was separated from a yeast extract by Karl Folkers, Carl Hoffman, and several others at Merck; while Huff and his associates confirmed mevalonic acid was an intermediary in cholesterol biosynthesis. In 1959, the HMG-CoA reductase enzyme (an important element of internal cholesterol production) was found by researchers at the Max Planck Institute. This discovery motivated scientists worldwide to seek an effective inhibitor of this enzyme.

By 1976, Akira Endo isolated the first inhibitor (Compactin, ML-236B) from the fungus, Penicillium citrinium in Sankyo, Japan. In 1979, Hoffman and colleagues isolated lovastatin from a strain of the fungus Aspergillus terreus. While devloping and doing research on lovastatin, Merck scientists synthetically captured a more potent HMG-CoA reductase inhibitor from a fermentation product of Aspergillus terreus, which became known as MK-733 (later to be named simvastatin).

Uses

Simvastatin is a powerful lipid-lowering drug that can lower decreased density lipoprotein (LDL) levels by up to 50%. It is prescribed in doses of 5 mg up to 80 mg. High doses (160 mg) have been found to be too toxic, while having only minimal effect in terms of lipid lowering. There is no recorded change in HDL and triglyceride levels.

From new found research it has become evident that simvastatin and other statins work to stop the progression of atherosclerosis beyond effects on LDL. Many explanations have been offered, for example its inhibitory effect on macrophages in the atherosclerotic plaque lesions.

In a non-randomized study, simvastatin cut the risk in half of developing dementia or Parkinson's disease.

Interactions

Grapefruit possesses the flavanones naringenin and bergamottin, which work to stop the liver cytochrome P450 3A4. This in turn slows metabolization of simvastatin and a large number of other drugs. Therefore, patients taking simvastatin should restrict their intake of grapefruit and grapefruit-containing products.

Discovery Today editorial, 2005.

Sales

Prior to having U.S. patent protection removed, simvastatin was Merck & Co.’s best selling drug and second best selling cholesterol lowering drug on the planet; it amassed 4.3 billion dollars in sales during 2005. Zocor had an original patent expiration date of January 2006 and as allowed extension by the United States Food and Drug Administration (FDA), with a continuance set to expire on June 23, 2006. The FDA allowed the patent extension after Merck & Co, Inc. sent in data from studies of the drug’s beneficial effect on children, a move typically used by drug companies to increase exclusiveness.

Normally, Merck & Co. would have been poised for a sharp decrease in sales after the generic versions of simvastatin arrived on the market; however, Merck has cut the price of Zocor drastically in an effort to net sales that would have otherwise gone to their generic counterparts. At least two major U.S. health insurers, UnitedHealthcare and WellPoint, are now providing Zocor to their members who have generic copays.

In addition, since Merck & Co. itself makes at least some variants of Dr. Reddy's authorized generic simvastatin. Merck & Co. is also set to profit from the Dr. Reddy's version. An 80 mg, 30-count bottle of Dr. Reddy's simvastatin obtained July 6, 2006, states it is manufactured by Merck Sharp & Dohme (Merck & Co.'s name outside the US to avoid conflicts with Merck KGaA) in the UK, just like 80 mg Zocor, and has a Merck & Co. logo on the bottom; except for not having the "80" on one side, the tablets are visually identical to 80 mg Zocor, including "543" on the other side which is the key component of the National Drug Code for 80 mg Zocor.

By 1976, Akira Endo isolated the first inhibitor (Compactin, ML-236B) from the fungus, Penicillium citrinium in Sankyo, Japan. In 1979, Hoffman and colleagues isolated lovastatin from a strain of the fungus Aspergillus terreus

Brought to you by the official UK simvastatin website.