Science · 1972 · 262 citations · 195 references
Life SciencesPharmacologyToxicologyEnvironmental ToxicologyEnzymologyMetabolismCytochrome P450-mediated MetabolismDrug-metabolizing EnzymesEnzyme InhibitionHepatic MetabolismMetabolic PathwaysMetabolism InteractionsDrug-enzyme InteractionsDrug-liver InteractionsHepatic Metabolism InteractionsLiver Microsomal MetabolismMetabolic Disruption By Environmental ToxicantsMetabolic Enzyme InhibitionMetabolism-based InteractionsMicrosomal Enzyme-mediated Metabolism
Metabolic interactions among drugs, insecticides, food additives, carcinogenic hydrocarbons, and other environmental chemicals arise from liver microsomal enzymes that can be stimulated or inhibited by co‑administered substances, a concept first identified in the 1950s. This research aims to inform safety and efficacy evaluations of drugs and environmental chemicals and to guide future studies. Examples of these interactions are provided.
It is evident that metabolic interactions can occur among drugs, insecticides, food additives, carcinogenic hydrocarbons, and a variety of environmental chemicals. A common denominator governing these effects is the versatile nature of the liver microsomal enzymes that metabolize chemicals with diverse structures and biological activities, and the fact that these enzymes can be stimulated or inhibited by other chemicals administered simultaneously. The discovery of these particular enzymes in the 1950's laid the groundwork for the current research on metabolic interactions. Such research provides information that is helpful in the evaluation of the safety and efficacy of drugs and environmental chemicals, and suggests new directions for further research. Some examples are as follows.
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Polychlorinated Biphenyls in the Global Ecosystem
Robert W. Risebrough, P. RIECHE, David B. Peakall et al. · Nature · 1968 · 738 citations
Nitrosamines as Environmental Carcinogens
William Lijinsky, Samuel S. Epstein · Nature · 1970 · 674 citations
Medicine, Pharmacology, Toxicology +12