Comparison of properties of four inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
Four inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase have been approved for treatment of hypercholesterolemia. Three of these are fungal metabolites or derivatives thereof: lovastatin, simvastatin, and pravastatin. The fourth, fluvastatin, is totally synthetic. Its structure, containing a fluorophenyl-substituted indole ring, is distinct from that of the fungal metabolites. Lovastatin and simvastatin are administered as prodrugs, which undergo in vivo transformation to active inhibitory forms; fluvastatin and pravastatin are administered as active agents. The HMG-CoA reductase inhibitors are all effective in reducing plasma concentrations of low density lipoprotein. They have differing pharmacokinetic properties, which may be of importance in some patients. All of these drugs are very well tolerated, and there do not appear to be major differences in toxicity or adverse effects. When LDL reductions > 30% are needed, simvastatin is the most cost-effective HMG-CoA reductase inhibitor. However, these drugs are most commonly used in dosages that reduce LDL-C by 20-30%. For this degree of LDL reduction, fluvastatin is the most cost-effective HMG-CoA reductase inhibitor.
Blum
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Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York.
D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000737:chemistry* / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use; D001711:Biotransformation; D003365:Costs and Cost Analysis; D004347:Drug Interactions; D004361:Drug Tolerance; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors