Donglu Zhang & Mingshe Zhu 
Drug Metabolism in Drug Design and Development 
Basic Concepts and Practice

The essentials of drug metabolism vital to developing new
therapeutic entities

Information on the metabolism and disposition of candidate drugs is
a critical part of all aspects of the drug discovery and
development process. Drug metabolism, as practiced in the
pharmaceutical industry today, is a complex, multidisciplinary
field that requires knowledge of sophisticated analytical
technologies and expertise in mechanistic and kinetic enzymology,
organic reaction mechanism, pharmacokinetic analysis, animal
physiology, basic chemical toxicology, preclinical pharmacology,
and molecular biology. With chapters contributed by experts in
their specific areas, this reference covers:

* Basic concepts of drug metabolism

* The role of drug metabolism in the pharmaceutical industry

* Analytical techniques in drug metabolism

* Common experimental approaches and protocols

Drug Metabolism in Drug Design and Development emphasizes practical
considerations such as the data needed, the experiments and
analytical methods typically employed, and the interpretation and
application of data. Chapters highlight facts, common protocols,
detailed experimental designs, applications, and limitations of
techniques.

This is a comprehensive, hands-on reference for drug metabolism
researchers as well as other professionals involved in pre-clinical
drug discovery and development.

Table of Content

Preface.

Contributors.

Part I: Basic Concepts of Drug Metabolism.

1. Overview: Drug Metabolism in the Modern Pharmaceutical
Industry (Scott J. Grossman)

2. Oxidative, Reductive, and Hydrolytic Metabolism of Drugs (F.
Peter Guengerich)

3. Conjugative Metabolism of Drugs (Rory Remmel, Swati Nagar and
Upendra Argikar)

4. Enzyme Kinetics (Timothy S. Tracy)

5. Metabolism-Mediated Drug-Drug Interactions (Hongjian Zhang,
Michael W. Sinz, and A. David Rodrigues)

6. Drug Transporters in Drug Disposition, Drug Interactions, and
Drug Resistance (Cindy Q. Xia, Johnny J. Yang, and Suresh K.
balani)

7. Regulatory Considerations of Drug Metabolism and Drug
Interaction Studies (Xiaoxiong Wei and Mingshe Zhu)

Part II: Role of Drug Metabolism in the Pharmaceutical
Industry.

8. Drug Metabolism Research as an Integral Part of the Drug
Discovery Process (W. Griffith Humphreys)

9. Role of Drug Metabosim in Drug Development (Ramaswamy Iyer
and Donglu Zhang)

Part III: Analytical techniques in Drug Metabolism.

10. Applications of Liquid Radiochromatography Techniques in
Drug Metabolism Studies (Mingshe Zhu, Weiping Zhao, and W. Griffith
Humphreys)

11. Application of Liquid Chromatogrpahy/Mass Spectrometry for
Metabolite Identification (Shuguang Ma and Swapan K. Chowdhury)

12. Introductin to NMR and Its Application in Metabolite
Structure Determination (Xiaohua Huang, Robert Powers, Adrienne
Tymiak, Robert Espina, and Vikram Roongta)

Part IV: Common Experimental Approaches and
Protocols.

13. Determination of Metabolic Rats and Enzyme Kinetics (Zhi-Yi
Zhang and Laurence S. Kaminsky)

14. Protocols for Assessment of In vitro and In vivo
Bioactivation Potential of Drug Candidates (Zhoupeng Zhang and
Jinping Gan)

15. Reaction Phenotyping (Susan Hurst, J. Andrew Williams, and
Steven Hansel)

16. Analysis of In vitro Cytochrome P450 Inhibition in Drug
Discovery and Development (Magang Shou and Renke Dai)

17. Testing Drug Candidates for CYP3A4 Induction (Gang Luo,
Liang-Shang Gan, and Thomas M. Guenthner)

18. ADME Studies in Animals and Humans: Experimental Design,
Metabolite Profoling and Identification, and Data Presentation
(Donglu Zhang and S. Nilgun Comezoglu)

Index.

About the author

Donglu Zhang, Ph D, is a senior scientist in the
Biotransformation Depart-ment at Bristol-Myers Squibb. His research
interests include metabolite characterization, drug metabolism
enzymology, LC/MS methodologies, and microbial
biotransformation.

MINGSHE ZHU, Ph D, is a drug metabolism scientist with more than
ten years of experience in drug discovery and development. His
research interests include metabolic activation, LC/MS technology,
and regulatory drug metabolism.

W. Griffith Humphreys, Ph D, is the Director of the
Biotransformation Department at Bristol-Myers Squibb. His research
interests include optimizationof ADME properties, metabolic
activation, and new methodologies for metabolite
characterization.