Clinical and toxicological consequences of the inductive potential of ethanol.
Variability in drug metabolism is an important factor that accounts for individual responsiveness to xenobiotics. Enzyme induction which leads to a more rapid elimination of foreign compounds and to a more extensive formation of potentially active metabolites significantly contributes to large interindividual variability in drug effects. Ethanol is consumed worldwide in tremendous amounts and is an effective inducer of hepatic drug metabolism, especially involving pathways accomplished by the CYP2E1 isoform of the cytochrome P-450 (CYP) superfamily. Therefore, whenever xenobiotics that are substrates of CYP2E1, such as chlorzoxazone, paracetamol (acetaminophen), halothane, enflurane, methoxyflurane, sevoflurane and many organic solvents (e.g. aniline, trichloroethylene), are taken by an individual who is also chronically consuming ethanol, the accelerated metabolism of these agents and their clinical impact (e.g. decrease in drug activity) and toxicological impact (accumulation of active metabolites) have to be considered. Consequently, in the assessment of drug disposition and action the history of ethanol intake should be carefully evaluated.
Klotz
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Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany.
Ammon
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D001711:Biotransformation; D002986:Clinical Trials as Topic; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism
D004364:Pharmaceutical Preparations; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1