ADME-Enabling Technologies in Drug Design and Development

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