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HMG-CoA Reductase Inhibitors (Statins)

Cholesterol is an essential component of all mammals’ organs and the precursor of all the steroid hormones, but it also plays in cardiovascular disease because of elevated cholesterol levels in the plasma. These Statins inhibit the action of enzyme HMG-CoA reductase (3-hydroxy-3-methylglutaryl coenzyme A reductase) that catalyzes the rate-limiting step in cholesterol biosynthesis, resulting in the reduction of low-density-lipoprotein (LDL) and total cholesterol levels.1,2) Especially in statins, atorvastatin calcium salt trihydrate (1) is a most potent inhibitor because it has a long half-life and metabolites which also play a role as an HMG-CoA reductase inhibitor. Statins 3, 4 and 6 are pro-drugs that are activated by in vivo hydrolysis of the lactone ring. Many statins are metabolized by cytochrome P450 3A4 (CYP3A4) while fluvastatin (2) is metabolized by CYP2C9.2b,c) The features of each statin can be found in the references.3)

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