Cerivastatin Sodium

Cerivastatin sodium is a synthetic, enantiomerically pure pyridine derivative that acts as a highly potent competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. The drug is rapidly and completely absorbed from the gastrointestinal tract, reaching peak plasma concentrations within 2 to 3 hours, with an elimination half-life of 2 to 3 hours and absolute oral bioavailability of 60 percent. Cerivastatin demonstrates high liver selectivity, with a steady-state volume of distribution of approximately 0.3 L/kg indicating moderate tissue penetration, while preclinical studies confirm high affinity for hepatic tissue, the target site of action. The drug is exclusively cleared via metabolism, undergoing two main oxidative biotransformation reactions: demethylation of the benzylic methyl ether moiety and stereoselective hydroxylation of the 6-isopropyl substituent. All three resulting metabolites remain active HMG-CoA reductase inhibitors with potency similar to the parent compound.

Fig. 1 Mechanistic explanation of the interactions of cerivastatin with cytochrome P450 (CYP) 3A4 inhibitors. (Mück W. 2000)