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EFFECTS OF INTERFERON‐INDUCING AGENTS ON HEPATIC CYTOCHROME P‐450 DRUG METABOLIZING SYSTEMS *
Author(s) -
Mannering Gilbert J.,
Renton Kenneth W.,
Azhary Rokea el,
Deloria Laurel B.
Publication year - 1980
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1980.tb20631.x
Subject(s) - cytochrome , drug metabolism , drug , pharmacology , interferon , immune system , chemistry , biology , biochemistry , immunology , enzyme
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.