CLINICAL PHARMACOKINETICS OF 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE INHIBITORS

3-Hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase is the key e nzyme of cholesterol synthesis. HMG-CoA reductase inhibitors are poten t reversible inhibitors of this enzyme, which act by competing for the substrate HMG-CoA. This review is mainly devoted to the 4 main HMG-Co A reductase inhibitors used today: lovastatin, simvastatin. pravastati n and fluvastatin, Depending upon the dosage, these drugs are able to reduce plasma cholesterol levels by more than 40%. After absorption, e ach undergoes extensive hepatic first-pass metabolism. Up to 5 primary metabolites are formed, some of which are active inhibitors. The elim ination half-lives vary from 0.5 to 3.5 hours and excretion is mainly via the faeces. A limited number of drug interactions has been reporte d. increases in liver enzymes and muscle creatine kinase activity are among the most severe adverse effects. These powerful drugs should be reserved for patients with high plasma cholesterol levels and/or those with cardiovascular disease. New therapeutic approaches to atheroscle rosis are currently under investigation. HMG-CoA reductase inhibitors are the cornerstone of this research.