Drug Metabolism - Towards the Next Milennium

Author: N. J. Gooderham
Published: January 1998
Publisher: I O S Press, Incorporated
ISBN: 9051993781
Hardcover Book
Number of Pages: 213

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With its roots in the last century and currently exploiting the technology of today, the science of drug metabolism has made significant contributions to our understanding of chemico-biological interactions. 'Drug Metabolism: Towards the next Millennium,' reviews past successes and failures within the science and attempts to predict new directions. Each of the chapters of this book deals with an aspect of xenobiotic metabolism which has featured prominently in the development of the discipline. The authors, all acknowledged experts, have produced personal reviews which provide an insight of the area and an indication of where the challenges are likely to lie in the next century. The volume is testimony to the breadth and depth of research into xenobiotic metabolism and covers the chemistry and enzymology of xenobiotic metabolism, enzyme modeling and structure activity relationships, pharmacokinetics, the use of recombinant gene technology, site directed mutagenesis, transgenic and gene knockout models, new analytical techniques including capillary electrophoresis-mass spectrometry, accelerator mass spectrometry, high throughput analysis toxicological assessment, pharmacogenetics, drug development and therapeutics. With new chemical entities constantly emerging and requiring evaluation, the concepts and techniques developed in this book will help focus future lines of investigation and help set priorities in the next millennium.

Table of Contents:

Foreword
Molecular Modelling in Drug Metabolism: The Cytochromes P450 1
Recombinant DNA Methods in Drug Metabolism and Toxicology 13
Oxidation at Carbon via Cytochrome P450 CYP1B1 24
Catalytic Mechanism of FMO-Catalysed N- and S-Oxidations 30
Oxidation of Carbon via Molybdenum Hydroxylases 39
The Role of Amine Oxidases in Xenobiotic Metabolism 53
Oxidation and Reduction of Nitrogen via CYP450: Importance of the Reduction of Genotoxic N-Hydroxylated Functional Groups 59
Reductive Metabolism: its Application in Prodrug Activation 72
Glucuronidation: Towards the Next Millennium 80
Sulfotransferases and the Biology of Sulfation 89
Glutathione Conjugation 101
Clinical Aspects of Polymorphic Drug Metabolism 109
Towards the Next Millennium: Pharmacogenetics 119
Metabolism and Genotoxicity of Food-Derived Heterocyclic Amines 127
High Throughput Drug Metabolism 137
The Use of Kinetic and Metabolic Predictions in Drug Development 144
Mass Spectrometry in Drug Metabolism 159
Accelerator Mass Spectrometry - A New Tool for Drug Metabolism Studies 175
Overcoming Sample Loading Limitations of On-Line Capillary Electrophoresis-Mass Spectrometry in the Analysis of Drug Metabolites and Xenobiotic Toxins 188
Enantiospecific Bioanalysis: Techniques and Applications 196
Author Index 213

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