Drug interactions of the statins and consequences for drug selection

Cholesterol-lowering drugs such as HMG-CoA reductase inhibitors ("statins") are increasingly used in hypercholesterolemic patients who suffer from multiple concomitant diseases, and are therefore taking multiple drugs. The statins do not differ in their mechanism of action (pharmacodynamics), but there are differences in the affinity to the target enzyme as well as differences in pharmacokinetic properties, which need to be considered when choosing a statin for a specific patient. The most critical side effect of statins is development of myopathy, which becomes evident as muscle pain, weakness, and elevation of serum creatine kinase activity. The incidence of myopathy is usually low. However, myopathy and rhabdomyolysis are more frequent when statins are combined with other drugs that inhibit cytochrome P450-dependent metabolism of statins in the liver (e.g., itraconazole, erythromycin). Drug interactions can thus significantly increase the risk associated with statin therapy. Oral bioavailability of the statins varies considerably. Besides the absolute rate of oral bioavailability, it is important to know the relative difference between intestinal absorption rate and rate of oral bioavailability in order to assess the potential for drug-drug interactions. Statins that are not metabolized by a single cytochrome P450 isoenzyme, and have a high bioavailability, are the least prone to drug interactions.