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The Importance of Cytochrome P450 3A Enzymes in Drug Metabolism

  • Conference paper
Assessment of the Use of Single Cytochrome P450 Enzymes in Drug Research

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 13))

Abstract

The biotransformation of drugs in the body has been appreciated for over a century (Keller 1842; Baumann and Preusse 1879; Jaffe 1879). Cytochrome P450 (P450) enzymes were reported more than 50 years ago (Mueller and Miller 1953; Brodie et al. 1958), and they are now recognized to be the major catalysts involved in the metabolism of drugs, steroids, carcinogens, pesticides, and pollutants (see entire January 1992 issue of FASEB Journal). There has been considerable interest in being able to understand and predict transformation of xeno-biotic chemicals in fields such as drug metabolism and chemical carcinogenesis. With appreciation of the increasing complexity of P450 enzymes in the 1970s it was unclear as to whether the biotransformation of xenobiotics could ever be comprehended in terms of a limited number of P450 enzymes. In the 1980s there was extensive characterization of many of the human P450s. Many drug oxidations can now be attributed to a few, major P450 enzymes. Several lines of evidence suggest that the enzyme P450 3A4 is, on the average, the major P450 present in human liver, and that small intestine plays a significant role in the metabolism of many drugs.

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Authors
  1. F. P. Guengerich
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  2. E. M. J. Gillam
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  3. M. V. Martin
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  4. T. Baba
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  5. B.-R. Kim
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  6. T. Shimada
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  7. K. D. Raney
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  8. C.-H. Yun
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Editors and Affiliations

  1. Department of Biochemistry, Vanderbilt University School of Medicine, 37232, Nashville, TN, USA

    M. R. Waterman

  2. Institute of Pharmacokinetics, Schering AG, 13342, Berlin, Germany

    M. Hildebrand

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© 1994 Springer-Verlag Berlin Heidelberg

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Guengerich, F.P. et al. (1994). The Importance of Cytochrome P450 3A Enzymes in Drug Metabolism. In: Waterman, M.R., Hildebrand, M. (eds) Assessment of the Use of Single Cytochrome P450 Enzymes in Drug Research. Ernst Schering Research Foundation Workshop, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-03019-6_9

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  • DOI: https://doi.org/10.1007/978-3-662-03019-6_9

  • Publisher Name: Springer, Berlin, Heidelberg

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