ABSTRACT
Adverse drug reactions can result from drug-drug interactions. Examples are plentiful: Fatalities have been reported for patients taking the antihistamine terfendadine and the antifungal ketoconazole. We now know that this is due to the inhibition of the major CYP isoform for terfenadine metabolism, CYP3A4, by
ketoconazole. The result is the elevation of plasma terfenadine to a cardiotoxic level. Another example is the decrease in effectiveness of oral contraceptives in women who were also administered rifampin. Rifampin is now known to enhance the metabolism of
EE2, the active ingredient of oral contraceptives, thereby lowering the plasma level of EE2 to nontherapeutic levels. Drug-drug interactions therefore can have both toxicological and pharmacological consequences. An optimized drug should have minimum drug-drug interaction potential.
