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  • Title: [Extended worldwide experience. HMG-CoA reductase inhibitors: lovastatin and simvastatin].
    Author: Mantell G.
    Journal: Therapie; 1992; 47(2):161-4. PubMed ID: 1412144.
    Abstract:
    Lovastatin and simvastatin are the first licensed compounds of a potent new class of lipid lowering drugs whose mechanism of action is to inhibit HMG-CoA reductase, a rate-limiting enzyme in the cholesterol biosynthetic pathway in the liver. Inhibition of cholesterol synthesis leads to upregulation of LDL-receptors in the liver and subsequent increased LDL clearance. Both agents are pro-drugs (lactones) which undergo extensive first-pass hepatic metabolism to the beta-hydroxyl acid form. These drugs are liver specific and have low systemic exposure as open-acid forms (plasma concentration < 5% of oral dose). Thus, theoretically both drugs have low potential for systemic adverse events. They are potent and effective agents for the treatment of primary hypercholesterolemia. The adverse experiences reported for both drugs demonstrate an excellent safety profile.
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