Molecular biological methods for characterizing drug-metabolizing enzymes in hepatic and extrahepatic tissues.
Drug metabolism influences the pharmacotoxicological properties of a vast array of compounds and is controlled by a complex system of drug-metabolizing enzymes. A thorough understanding of this system allows the more effective development of therapeutic drugs as well as a significant improvement of risk assessment. The early identification of optimal therapeutic problems relating to drug metabolism could reduce the development costs for pharmaceuticals. Recently, techniques using transgenes have become available for this purpose. In these approaches the genetic information for the enzyme under investigation is expressed in vitro or in vivo, following gene transfer. This approach is called 'heterologous expression'. This article illustrates some examples in which molecular biological methods have been used to analyze those enzymes which control the pharmacotoxicological properties of drugs. Particular emphasis has been placed on the use of these methods to characterize extrahepatic drug-metabolizing enzymes such as those in the skin.
Friedberg
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Biomedical Research Centre, University of Dundee, Medical School, Ninewells Hospital, UK.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004274:DNA, Recombinant / Q000235:genetics; D014453:Glucuronosyltransferase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009928:Organ Specificity / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004274:DNA, Recombinant; D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase