Statins are a group of substances indicated to low
cholesterol blood level. These
substances are used as therapy for patients with primary
hypercholesterolemia. The first compound of this group was lovastatin,
which was developed by Merck Sharp & Dohme and got the approval from
the FDA on August 1987.
The second compound of this group to reach the market was
simvastatin and was approved by the FDA on December 1991. Also in
1991, a third molecule developed by Bristol Meyer Squibb/ Sankyo, got
the approval by the FDA (Pravastatin).
Lovastatin, simvastatin and pravastatin belong to the 1st
generation of statins, which are synthesized via a multi-stage fermentation
process originated from cultures of a strain of Aspergillus terreus.
Simvastatin is a pro-drug derivative of lovastatin. After
absorption, it undergoes rapid enzymatic hydrolysis of the lactone
ring to form the principal metabolite, simvastatin-β-hydroxyacid. This
metabolite acts as a potent, reversible, competitive inhibitor of
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which
catalyses the conversion of hydroxymethyl glutarate to mevalonate.
This conversion is an early and rate-limiting step in the biosynthesis
of cholesterol1.
Other HMG-CoA reductase inhibitors were developed afterwards, which
are considered the 2nd and 3rd statins generation and are produced by
chemical synthesis.
Simvastatin has been until now used mainly to reduce cholesterol
and tryglycerides level. However, a recent report from MRC/BHF Heart
Protection Study published by The Lancet2
presents the results of a randomised trial that evaluates the effect
of cholesterol-lowering with simvastatin in preventing vascular
events. This study indicates a clear benefit in using simvastatin in
selected populations with myocardial infraction and stroke risk for
prevention.
1
Simvastatin; Dean K. Ellison, William D. Moore,
Catherine R. Petts; Analytical Profiles of Drug Substances and
Excipients; Volume 22; 1993.
2
The Lancet; Volume 360; July 6, 2002.
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