Optimizing the pharmacology of statins: characteristics of rosuvastatin.

Rosuvastatin (Crestor, AstraZeneca) is a new synthetic statin that exhibits a number of highly desirable pharmacologic characteristics. The drug has a high affinity for the active site of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and exhibits greater potency in inhibiting enzyme activity and cholesterol synthesis in vitro than other statins. The effects of rosuvastatin are selective for hepatic cells, and there is minimal uptake of the drug by nonhepatic tissues. The vast majority of biologic activity of the drug is associated with the parent compound, which does not appear to undergo extensive metabolism. Hepatic metabolism appears to be minimal, and there is little evidence of metabolic interaction with cytochrome P450 3A4. In an early-phase study, rosuvastatin produced large and dose-related decreases in low-density lipoprotein (LDL) cholesterol of up to 65% in hypercholesterolemic patients. Rosuvastatin should constitute an important addition to current lipid-lowering interventions.