Cytochrome P450 isoenzymes--importance for the internist

The studies with CYP isoenzymes give hope that in the near future it will be possible to predict the clinical pharmacokinetics of drugs, if their oxidation can be assigned to the activity of one or more well-characterized CYP isoenzymes (or if their metabolism is catalyzed by other well-studied enzymes). This strategy will reduce animal experimentation. Interindividual variability in drug metabolism translates into variability in drug efficacy and toxicity. Establishing the status of drug-metabolizing enzymes will therefore assist in making predictions of pharmacologic and toxicologic responses to drugs. Many clinically relevant drug-drug interactions can now be readily rationalized in terms of the substrate and inhibitor specificities of individual human CYP isoenzymes. The next 5 years should reveal whether selective inhibitors of xenobiotic-metabolizing CYP's can be used therapeutically in the treatment or prevention of cancer and various endocrine disorders, in analogy to the use of influencing steroidogenic CYP's.