ADME-Enabling Technologies in Drug Design and Development

Zhang, Donglu / Surapaneni, Sekhar (Herausgeber)

1. Auflage Mai 2012
624 Seiten, Hardcover
Praktikerbuch

ISBN: 978-0-470-54278-1

John Wiley & Sons

Kurzbeschreibung

This book comprehensively covers the state-of-the-art and cutting-edge technologies in an integrated fashion for applications in ADME studies of small molecular drugs. Each chapter provides descriptions of the technologies, application scope and limitations, optimal conditions for intended results, protocols, case studies, and future developments. By concisely describing these technologies, the book provides a useful tool for drug metabolism scientists and as a reference for scientists in the fields of pharmacology, medicinal chemistry, pharmaceutics, toxicology, bioanalytical science in academia and industry.

Weitere Versionen

A comprehensive guide to cutting-edge tools in ADME research

The last decade has seen tremendous progress in the development of analytical techniques such as mass spectrometry and molecular biology tools, resulting in important advances in drug discovery, particularly in the area of absorption, distribution, metabolism, and excretion (ADME).

ADME-Enabling Technologies in Drug Design and Development focuses on the current state of the art in the field, presenting a comprehensive review of the latest tools for generating ADME data in drug discovery. It examines the broadest possible range of available technologies, giving readers the information they need to choose the right tool for a given application, a key requisite for obtaining favorable results in a timely fashion for regulatory filings. With over thirty contributed chapters by an international team of experts, the book provides:
* A thorough examination of current tools, covering both electronic/mechanical technologies and biologically based ones
* Coverage of applications for each technology, including key parameters, optimal conditions for intended results, protocols, and case studies
* Detailed discussion of emerging tools and techniques, from stem cells and genetically modified animal models to imaging technologies
* Numerous figures and diagrams throughout the text

Scientists and researchers in drug metabolism, pharmacology, medicinal chemistry, pharmaceutics, toxicology, and bioanalytical science will find ADME-Enabling Technologies in Drug Design and Development an invaluable guide to the entire drug development process, from discovery to regulatory issues.

FOREWORD xxi
Lisa A. Shipley

PREFACE xxv
Donglu Zhang and Sekhar Surapaneni

CONTRIBUTORS xxvii

PART A ADME: OVERVIEW AND CURRENT TOPICS 1

1 Regulatory Drug Disposition and NDA Package Including MIST 3
Sekhar Surapaneni

References 12

2 Optimal ADME Properties for Clinical Candidate and Investigational New Drug (IND) Package 15
Rajinder Bhardwaj and Gamini Chandrasena

References 25

3 Drug Transporters in Drug Interactions and Disposition 29
Imad Hanna and Ryan M. Pelis

References 46

4 Pharmacological and Toxicological Activity of Drug Metabolites 55
W. Griffith Humphreys

References 63

5 Improving the Pharmaceutical Properties of Biologics in Drug Discovery: Unique Challenges and Enabling Solutions 67
Jiwen Chen and Ashok Dongre

References 75

6 Clinical Dose Estimation Using Pharmacokinetic/Pharmacodynamic Modeling and Simulation 79
Lingling Guan

References 93

7 Pharmacogenomics and Individualized Medicine 95
Anthony Y.H. Lu and Qiang Ma

Disclaimer 105

Contact Information 105

References 105

8 Overview of Drug Metabolism and Pharmacokinetics with Applications in Drug Discovery and Development in China 109
Chang-Xiao Liu

References 125

PART B ADME SYSTEMS AND METHODS 129

9 Technical Challenges and Recent Advances of Implementing Comprehensive ADMET Tools in Drug Discovery 131
Jianling Wang and Leslie Bell

Acknowledgments 155

References 155

10 Permeability and Transporter Models in Drug Discovery and Development 161
Praveen V. Balimane, Yong-Hae Han, and Saeho Chong

References 167

11 Methods for Assessing Blood-Brain Barrier Penetration in Drug Discovery 169
Li Di and Edward H. Kerns

References 174

12 Techniques for Determining Protein Binding in Drug Discovery and Development 177
Tom Lloyd

Acknowledgment 185

References 185

13 Reaction Phenotyping 189
Chun Li and Nataraj Kalyanaraman

References 206

14 Fast and Reliable CYP Inhibition Assays 213
Ming Yao, Hong Cai, and Mingshe Zhu

References 230

15 Tools and Strategies for the Assessment of Enzyme Induction in Drug Discovery and Development 233
Adrian J. Fretland, Anshul Gupta, Peijuan Zhu, and Catherine L. Booth-Genthe

References 246

16 Animal Models for Studying Drug Metabolizing Enzymes and Transporters 253
Kevin L. Salyers and Yang Xu

Acknowledgments 271

References 271

17 Milk Excretion and Placental Transfer Studies 277
Matthew Hoffmann and Adam Shilling

References 289

18 Human Bile Collection for ADME Studies 291
Suresh K. Balani, Lisa J. Christopher, and Donglu Zhang

Acknowledgment 297

References 297

PART C ANALYTICAL TECHNOLOGIES 299

19 Current Technology and Limitation of LC-MS 301
Cornelis E.C.A. Hop

References 314

20 Application of Accurate Mass Spectrometry for Metabolite Identification 317
Zhoupeng Zhang and Kaushik Mitra

References 329

21 Applications of Accelerator Mass Spectrometry (AMS) 331
Xiaomin Wang, Voon Ong, and Mark Seymour

References 337

22 Radioactivity Profiling 339
Wing Wah Lam, Jose Silva, and Heng-Keang Lim

Acknowledgments 349

References 349

23 A Robust Methodology for Rapid Structure Determination of Microgram-Level Drug Metabolites by NMR Spectroscopy 353
Kim A. Johnson, Stella Huang, and Yue-Zhong Shu

References 362

24 Supercritical Fluid Chromatography 363
Jun Dai, Yingru Zhang, David B. Wang-Iverson, and Adrienne A. Tymiak

References 376

25 Chromatographic Separation Methods 381
Wenying Jian, Richard W. Edom, Zhongping (John) Lin, and Naidong Weng

References 396

26 Mass Spectrometric Imaging for Drug Distribution in Tissues 401
Daniel P. Magparangalan, Timothy J. Garrett, Dieter M. Drexler, and Richard A. Yost

References 414

27 Applications of Quantitative Whole-Body Autoradiography (QWBA) in Drug Discovery and Development 419
Lifei Wang, Haizheng Hong, and Donglu Zhang

References 433

PART D NEW AND RELATED TECHNOLOGIES 435

28 Genetically Modified Mouse Models in ADME Studies 437
Xi-Ling Jiang and Ai-Ming Yu

References 448

29 Pluripotent Stem Cell Models in Human Drug Development 455
David C. Hay

References 458

30 Radiosynthesis for ADME Studies 461
Brad D. Maxwell and Charles S. Elmore

References 471

31 Formulation Development for Preclinical in vivo Studies 473
Yuan-Hon Kiang, Darren L. Reid, and Janan Jona

References 482

32 In vitro Testing of Proarrhythmic Toxicity 485
Haoyu Zeng and Jiesheng Kang

References 492

33 Target Engagement for PK/PD Modeling and Translational Imaging Biomarkers 493
Vanessa N. Barth, Elizabeth M. Joshi, and Matthew D. Silva

References 508

34 Applications of iRNA Technologies in Drug Transporters and Drug Metabolizing Enzymes 513
Mingxiang Liao and Cindy Q. Xia

Acknowledgment 539

References 539

Appendix Drug Metabolizing Enzymes and Biotransformation Reactions 545
Natalia Penner, Caroline Woodward, and Chandra Prakash

Acknowledgment 562

References 562

Index 567

"This book fills time needs of ADME researchers and provides a fine reference book for scientists engaged in the areas of medicinal chemistry, pharmaceutics, bioanalytical sciences, pharmacology and toxicology in academia and pharmaceutical industry." (British Toxicology Society, 1 July 2013)

Donglu Zhang, PhD, is a Principal Scientist in Pharmaceutical Candidate Optimization at Bristol-Myers Squibb in Princeton, New Jersey. He has published seventy peer-reviewed articles, codiscovered the Mass Defect Filtering technique, and coedited two books.

Sekhar Surapaneni, PhD, is Director, DMPK, at Celgene Corporation in New Jersey. He has published extensively in peer-reviewed journals and is a member of ISSX and ACS.

D. Zhang, Bristol-Myers Squibb Pharmaceutical Research Institute