Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors (statins)

Eur J Clin Pharmacol. 2001 Aug;57(5):357-64. doi: 10.1007/s002280100329.

Abstract

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors (statins) are mainly considered for long-term use and often constitute part of a multiple-drug regime. Besides common adverse drug effects, such as nausea, abdominal discomfort and headaches, all statins harbour the risk of myopathy and fatal rhabdomyolysis. Usually, the frequency of myopathy is low but the incidence increases during concomitant drug therapy. Statins do not differ in their pharmacodynamic property. Therefore, the differences in their pharmacokinetic profiles, i.e. affinity for metabolising enzymes, constitute the rationale for choosing a specific statin especially for combination therapy. In order to point out harmful combinations of therapeutics, this review summarises the pharmacokinetic data of six clinically used statins (atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin and simvastatin) with special regard to metabolism and drug interactions. In summary, statins that lack a significant hepatic metabolism, i.e. pravastatin, or that are metabolised by more than one cytochrome P450 isoenzyme, i.e. fluvastatin, or whose metabolism is taken over by other cytochrome P450 isoenzymes in case of blockage of the main metabolising enzyme, i.e. cerivastatin, are the least prone to drug interactions. Nevertheless, in case of a specific concomitant drug therapy known to be associated with a higher risk of adverse events, i.e. cyclosporin A and statin, clinical symptoms of myopathy and biochemical data, such as increasing serum creatine phosphokinase, should be monitored carefully.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Atorvastatin
  • Drug Interactions
  • Drug Therapy, Combination
  • Fatty Acids, Monounsaturated / pharmacokinetics
  • Fluvastatin
  • Heptanoic Acids / pharmacokinetics
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / metabolism*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / metabolism
  • Indoles / pharmacokinetics
  • Lovastatin / pharmacokinetics
  • Pravastatin / pharmacokinetics
  • Pyridines / pharmacokinetics
  • Pyrroles / pharmacokinetics
  • Simvastatin / pharmacokinetics

Substances

  • Fatty Acids, Monounsaturated
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Pyridines
  • Pyrroles
  • Fluvastatin
  • Lovastatin
  • Atorvastatin
  • Simvastatin
  • cerivastatin
  • Pravastatin