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Encyclopedia of Drug Metabolism and Interactions, Volume 3, Pharmaceutical Science Applications

Encyclopedia of Drug Metabolism and Interactions, Volume 3, Pharmaceutical Science Applications

Alexander V. Lyubimov (Editor-in-Chief)

ISBN: 978-1-118-14976-8

Nov 2012

764 pages

Select type: Hardcover


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The ideal place to begin researching any question involving drug metabolism and interactions

The Encyclopedia of Drug Metabolism and Interactions provides essential support during all phases of drug development, from drug design to drug action and interaction within the human body. This six-volume work covers both preclinical and clinical aspects of drug metabolism and interactions. It also provides a wealth of toxicological, regulatory, and marketing information, all written and edited by leading international experts in the field.

By collecting and reviewing the current literature in the field in one expertly organized work, this encyclopedia is the ideal place to begin researching any question involving drug metabolism and interactions. Readers will find such important topics and working tools as:

  • Inhibited or induced enzymes and their impact on drug toxicity and altered response in both animal and human models
  • Effects of both genetic and non-genetic factors on drug metabolism
  • Relationships between a drug metabolism, its activation or inactivation, and a drug's potential toxicity/safety
  • Examples demonstrating all aspects of drug metabolism and interactions in silico, in vitro, in laboratory animals, and in humans
  • Methods and protocols enabling readers to perform seamless studies of metabolism and drug interactions

All articles are based on recent findings and standards of practice. By reviewing and contextualizing the current literature, the authors offer new perspectives on our current state of knowledge as well as future directions for research in drug metabolism and interactions. References at the end of each article serve as a gateway to the literature.

The Encyclopedia of Drug Metabolism and Interactions is recommended for researchers, physicians, and students at all levels. It introduces the basics to novices and explores the latest science and applications for more experienced investigators.

Contributors xi

Preface to the Encyclopedia xxv

Preface—Volume 3 xxix

PART V Drug Design and Development 1

1 When and How to Apply ADMET Principles to Drug

Discovery and Development 3
Dennis A. Smith

2 Molecular Challenges in Front-Loading Toxicity Testing of Anticancer Drugs in Drug Discovery 23
Dale E. Johnson and Sucha Sudarsanam

3 Role of ADME Studies in Selecting Drug Candidates: Dependence of ADME Parameters on Physicochemical Properties 43
Cornelis E. C. A. Hop

4 Effective Early Drug Development 87
Ihor Bekersky, Mark Walzer, Susan Reid MEd, and Dwain Tolbert

5 Identification of Drug Metabolites 121
Scott R. Obach, Deepak K. Dalvie, and Gregory S. Walker

6 Drug Bioactivation and Oxidative Stress 177
Hayley M. Webb, Sophie Regan, Daniel J. Antoine, Nicola Lane, Rachel J. Walsh, Abhishek Srivastava, Philip Starkey-Lewis, Craig Benson, Dominic P. Williams, Hugh Laverty, Christopher Goldring, and B. Kevin Park

7 Drug Metabolism in Drug Safety Evaluation 221
Thomas A. Baillie

PART VI Methods and Protocols for Prediction and Evaluation of Drug Metabolism and Drug Interaction Studies 245

8 In Silico Models of Drug Metabolism and Drug Interactions 247
Richard J. Dimelow, Paul D. Metcalfe, and Simon Thomas

9 Methods for Determination of Enzyme Kinetics and Metabolic Rates 287
Murali Subramanian and Timothy S. Tracy

10 Utility of Molecular-Based In Vitro Assays in Metabolic Liability of Drug Candidates 315
Ji Young Lee, Timothy A. Moeller, Rob Shipman, Alexis Kaushansky, and Jasminder Sahi

11 Applications Using Caco-2 and TC7 Cells for Drug Metabolism Studies 335
Eric Le Ferrec and Olivier Fardel

12 In Vitro Liver Systems to Study Induction/Inhibition: Prediction of In Vivo Metabolism and Drug–Drug Interactions 351
Hiroshi Komura and Masahiro Iwaki

13 Assessing the Hepatic Disposition and Toxicity of Xenobiotics Using Primary Hepatocytes 393
Jasminder Sahi, Cornelia Smith, LaHoma Easterwood, Susan Grepper, and Edward LeCluyse

14 Monoclonal Antibody Analyses of Microsomal Human Drug Metabolism and Multifunctional Cytochrome P450 447
Kristopher W. Krausz and Harry V. Gelboin

15 Precision-Cut Tissue Slices: A Suitable In Vitro System for the Study of the Induction of Drug-Metabolizing Enzyme Systems 467
Costas Ioannides and Brian G. Lake

16 The Impact of Solubility and Dissolution Assessment on Formulation Strategy and Implications for Oral Drug Disposition 493
Jochem Alsenz

17 Integrated Approaches to Blood–Brain Barrier 563
Haojing Rong, Bo Feng, and Li Di

18 Why Do We Need In Vivo Models in Drug Metabolism? 591
Kevin Beaumont

19 Utility of Genetically Modified Animal Models for Drug Metabolism and Drug Transporters 617
Andrew Bessire, Kuresh Youdim, Susan Hurst, and Caroline A. Lee

Index 705