CLINICAL AND TOXICOLOGICAL CONSEQUENCES OF THE INDUCTIVE POTENTIAL OFETHANOL

Variability in drug metabolism is an important factor that accounts fo r individual responsiveness to xenobiotics. Enzyme induction which lea ds to a more rapid elimination of foreign compounds and to a more exte nsive formation of potentially active metabolites significantly contri butes 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. There fore, whenever xenobiotics that are substrates of CYP2E1, such as chlo rzoxazone, paracetamol (acetaminophen), halothane, enflurane, methoxyf lurane, sevoflurane and many organic solvents (e.g. aniline, trichloro ethylene), are taken by an individual who is also chronically consumin g ethanol, the accelerated metabolism of these agents and their clinic al impact (e.g. decrease in drug activity) and toxicological impact (a ccumulation of active metabolites) have to be considered. Consequently , in the assessment of drug disposition and action the history of etha nol intake should be carefully evaluated.