Bringing together nearly forty collaborators from academic and industrial laboratories, this reference furnishes an overview of the subject from a historical, kinetic, and chemical context. A source of expertise for a rapidly changing and expanding field, the book provides a framework for drug metabolism in drug discovery and development. Containing tables, drawings, photographs, and equations, it highlights the importance of pharmacokinetics and cytochrome P450, explains clearance, volume of distribution, sequential metabolism, and nonlinear kinetics, summarizes concepts of Phase 1 and 2 metabolites, evaluates tertiary amine metabolism and reactive metabolite chemistry, and more.
Table of Contents
FUNDAMENTAL ASPECTS OF DRUG METABOLISM
Pharmacokinetics of Drug Metabolites, P.C. Smith
Oxidative Metabolic Bioactivation of Xenobiotics, S. Mabic, K. Castagnoli, and N. Castagnoli, Jr.
Morphofunctional Aspects of the Hepatic Architecture: Functional and Subcellular Correlates, F.A. de la Iglesia, D.G. Robertson, and J.R. Haskins
The Cytochrome P450 Oxidative System, P.R. Ortiz de Montellano
Transformation Enzymes: Oxidative; Non-P450, A.E. Rettie and M.B. Fisher
Transformation Reactions: Glucuronidation, B. Burchell
FACTORS AFFECTING DRUG METABOLISM
Pharmacogenetics, A.K. Daly
Inhibition of Drug Metabolizing Enzymes: Molecular and Biochemical Aspects, F.P. Guengerich
Metabolic Drug Interactions, W.D. Hooper
Induction of Human Drug-Metabolizing Enzymes: Mechanisms and Implications, M.J.J. Ronis and M. Ingelman-Sundberg
Sites of Metabolism: Lung, G.S. Yost
Applications of Heterologous Expressed and Purified Human Drug-Metabolizing Enzymes: An Industrial Perspective, A.D. Rodrigues
In Vivo and In Vitro Recombinant DNA Technology as a Powerful Tool in Drug Development, T. Friedberg, C.J. Henderson, M.P. Pritchard, and C.R. Wolf
In Vitro Metabolism: Subcellular Fractions, S. Ekins, J. Mäenpää, and S.A. Wrighton
In Vitro Metabolism: Hepatocytes, M.W. Sinz
The Isolated Perfused Liver as a Tool in Drug Metabolism Studies, M. Kukan
Metabolic Models of Cytotoxicity, M. Pirmohamed and B.K. Park
In Vitro Metabolism: FMO and Related Oxygenations, J.R. Cashman
Applications of Caco-2 Cells in Drug Discovery and Development, S. Yee and W.W. Day
The Role of Nuclear Magnetic Resonance Spectroscopy in Drug Metabolism, I.D. Wilson, J.K. Nicholson, and J.C. Lindon
METABOLISM IN DRUG DISCOVERY AND DEVELOPMENT
Preclinical Drug Metabolism Studies and Strategies, P.B. Inskeep and W.W. Day
Clinical Drug Metabolism Studies, W.F. Pool
"In this excellent book, the contributions of over 40 respected authors drawn from academia and industry provide a wide-ranging, informative, and highly readable account of drug metabolism from its principles to its current applications.
"This volume clearly has a place as a textbook for those studying drug metabolism, and the strong practical emphasis should also make it a valuable reference for those working in the area. For chemists whose work involves and interaction with, and understanding of, the discipline of drug metabolism, this book is highly recommended."
-Journal of the American Chemical Society
"…a most useful book for those interested in drug metabolism."
- Journal of Medicinal Chemistry
"…no doubt many readers will find inspiration and much information in the various chapters….
"…offers a wealth of information on drug metabolism."