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

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors (stati ns) 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 myopath y and fatal rhabdomyolysis. Usually, the frequency of myopathy is low but t he incidence increases during concomitant drug therapy. Statins do not diff er in their pharmacodynamic property. Therefore, the differences in their p harmacokinetic profiles, i.e. affinity for metabolising enzymes, constitute the rationale for choosing a specific statin especially for combination th erapy. In order to point out harmful combinations of therapeutics, this rev iew summarises the pharmacokinetic data of six clinically used statins (ato rvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin and simvastat in) with special regard to metabolism and drug interactions. In summary, st atins that lack a significant hepatic metabolism, i.e. pravastatin, or that are metabolised by more than one cytochrome P-450 isoenzyme, i.e. fluvasta tin, or whose metabolism is taken over by other cytochrome P-450 isoenzymes in case of blockage of the main metabolising enzyme, i.e. cerivastatin, ar e the least prone to drug interactions. Nevertheless, in case of a specific concomitant drug therapy known to be associated with a higher risk of adve rse events, i.e. cyclosporin A and statin, clinical symptoms of myopathy an d biochemical data, such as increasing serum creatine phosphokinase, should be monitored carefully.