Differential metabolism of statins: importance in drug-drug interactions

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is the key enzyme of cholesterol synthesis. HMG-CoA reductase inhibitors (statins) are potent, reversible inhibitors of this enzyme, which act by competing for the substrate, HMG-CoA. Six statins are now available: lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, and cerivastatin. The differences in the chemical structures of these agents are responsible for major differences in their pharmacokinetic properties. Pravastatin, a hydrophilic drug, is not significantly metabolized by the cytochrome P450 (CYP450) system, unlike the other statins, which are lipophilic. This unique quality of pravastatin affects its metabolism, potential for drug interactions, and side effect profile, compared with the other agents. The pharmacokinetic properties of the statins and how they affect the use of these agents in clinical practice are described here.