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
