COMPARISON OF PROPERTIES OF 4 INHIBITORS OF 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE

Four inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) red uctase have been approved for treatment of hypercholesterolemia. Three of these are fungal metabolites or derivatives thereof: lovastatin, s imvastatin, and pravastatin. The fourth, fluvastatin, Is totally synth etic. Its structure, containing a fluorophenyl-substituted indole ring , is distinct from that of the fungal metabolites. Lovastatin and simv astatin are administered as prodrugs, which undergo in vivo transforma tion to active inhibitory forms; fluvastatin acid pravastatin are admi nistered as active agents. The HMG-CoA reductase inhibitors are all ef fective in reducing plasma concentrations of low density lipoprotein. They have differing pharmacokinetic properties, which may be of import ance in some patients. All of these drugs are very well tolerated, and there do not appear to be major differences In toxicity or adverse ef fects. When LDL reductions >30% are needed, simvastatin is the most co st-effective HMG-CoA reductase inhibitor. However, these drugs are mos t commonly used in dosages that reduce LDL-C by 20-30%. For this degre e of LDL reduction, fluvastatin is the most cost-effective HMG-CoA red uctase inhibitor.