Is enzyme induction good for you? A problem of epidemiology and toxicology.
1. The discoveries that pre-treatment with certain compounds could increase the amounts of drug metabolizing enzymes present in the liver and that metabolism could enhance as well as reduce the toxicity of exogenous molecules were important milestones in toxicology. 2. Some clinically important adverse effects (vitamin D deficiency, reduced efficacy of oral contraceptives, interactions with anticoagulants) were found to be due to enzyme induction by, for example, anticonvulsants. 3. Intestinal enzymes are also inducible and can respond rapidly to individual compounds while the liver enzymes respond more slowly to the diet as a whole. Although promoting hepatic tumours in rats and mice, phenobarbitone does not have this effect in man because there seems to be a threshold for promotion which human use does not exceed. In neither case is there evidence that induction is harmful rather than adaptive in man. 4. As to the future, post-marketing surveillance will continue to be important in assessing the safety of new products, and knowledge of the metabolism and pharmacokinetics of new compounds in experimental animals and in man will assume greater importance. Finally, greater understanding of intracellular processes will pave the way to the study of toxicology at the macromolecular level and thus to critically assess the validity of the animal models currently used in toxicity testing.
McLean
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Department of Clinical Pharmacology, University Collge, London, UK.
D000818:Animals; D001711:Biotransformation; D004790:Enzyme Induction; D004812:Epidemiologic Methods; D006801:Humans; D008099:Liver / Q000201:enzymology*