September 21, 2001
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.