Effects of interferon-inducing agents on hepatic cytochrome P-450 drug metabolizing systems

Abstract

Duration and intensity of drug action are greatly influenced by the rates of which drugs are biotransformed by the cytochrome P-450-linked monooxygenase systems of the hepatic endoplasmic reticulum. Several interferon-inducing agents (poly rI.rC, tilorone, vaccines, viruses, endotoxin) are shown to markedly depress hepatic P-450 systems when administered to rodents. The interferon (IF) inducers that depress hepatic drug metabolism also modulate certain immune responses; it is therefore not known whether the depression of P-450 is due to IF per se or to the action of IF-inducing agents on one or more components of the immune system. The loss of cytochrome P-450 elicited by IF-inducing agents is accompanied by a perturbation of heme metabolism associated with the dissociation of heme from cytochrome P-450. The agents also cause losses of hepatic catalase and tryptophan 2,3-dioxygenase. These studies predict that viral infections, vaccinations, and treatment with IF-inducing agents will be shown to seriously impair the metabolism of drugs in humans.