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Alternatives to Laboratory Animals - ATLA

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Integration of In Vitro Approaches to Predict Drug Metabolism and Interaction in Man: An EU Validation Project

Magnus Ingelman-Sundberg

Extended Abstract


In the last decade, there have been important advances in therapeutics, which were derived from discoveries in molecular biology. The cytochromes P450 involved in human drug metabolism have been characterised. Their substrate specificities have been determined, and their polymorphic distribution has been established. Molecular biologists have defined both common and rare mutations that cause catalytic deficiencies, and much has been learned about the regulation of these enzymes in health and in disease. The tissue distribution of drug-metabolising enzymes and of metabolites has been characterised, and the mechanistic pathways of the enzymes have been identified.