ABSTRACT
This chapter focuses on those metabolic drug-drug interactions that have led or can lead to serious toxicological consequences in humans. It describes examples of metabolic drug-drug interactions that have caused serious toxicities. General aspects of the drug-drug interactions involving theophylline are similar to those described for warfarin, because it too is a drug with a narrow therapeutic index. Terfenadine and astemizole were removed from the market in 1997 and 1999, respectively, because of drug interactions that led to QT interval prolongation. Tacrolimus, a newer immunosuppressive agent related to cyclosporine, apparently, is subject to similar drug interactions as cyclosporine, though it has not been in use for long, and limited data are available. Felbamate apparently increases the metabolism of carbamazepine by heteroactivation of cytochrome P450 3A4, but toxicological consequences of this activation have not been documented.
