Predictive Approaches in Drug Discovery and Development

J. Andrew Williams, PHD, is Director of Translational Oncology at Pfizer Oncology.Richard Lalonde, PharmD, is Vice President and Global Head of Clinical Pharmacology at Pfizer.Jeffrey Koup, PharmD, is a consultant for PKPD modeling and the owner of Lakeside PKPD, LLC.David D. Christ, PHD, is a consultant with SNC Partners LLC.

• Preface xiAcknowledgments xiiiContributors xvPart I Biomarkers in Drug Discovery 11 The Importance of Biomarkers in Translational Medicine 3Joseph C. Fleishaker2 Validation of Biochemical Biomarker Assays used in Drug Discovery and Development: A Review ofChallenges and Solutions 23Gabriella Szekely-Klepser and Scott Fountain3 Proteomic Methods to Develop Protein Biomarkers 49Ruth A. VanBogelen and Diane Alessi4 Overview of Metabolomics Basics 79Qiuwei Xu and William H. SchaeferPart II Clinical Application of Biomarkers 1395 Vascular Biomarkers and Imaging Studies 141Karin Potthoff, Ulrike Fiedler, and Joachim Drevs6 Cardiovascular Biomarkers as Examples of Success and Failure in Predicting Safety in Humans 163Simon Authier, Michael K. Pugsley, Eric Troncy, and Michael J. Curtis7 The Use of Molecular Imaging for Receptor Occupancy Decision Making in Drug Development 189Ralph Paul Maguire8 Biosensors for Clinical Biomarkers 203Sara Tombelli and Marco MasciniPart III Regulatory Perspectives 2299 Regulatory Perspectives on Biomarker Development 231Rajanikanth Madabushi, Lawrence Lesko, and Janet Woodcock10 Perspectives from the European Regulatory Authorities 255Ian Hudson11 Use of Biomarker in Drug Development—Japanese Perspectives 269Yoshiaki Uyama, Akihiro Ishiguro, Harumasa Nakamura, and Satoshi ToyoshimaPart IV Predicting in Vivo 28912 In Vitro–In Vivo Correlations of Hepatic Drug Clearance 291R. Scott Obach13 The Potential of In Silico and In Vitro Approaches to Predict In Vivo Drug–Drug Interactions and ADMET/TOX Properties 307Kenneth Bachmann and Sean Ekins14 In Vitro–In Vivo Correlations in Drug Discovery and Development: Concepts and Applications inToxicology 331Rex Denton, Kimberly Brannen, and Bruce D. Car15 Assessing the Potential for Induction of Cytochrome P450 Enzymes and Predicting the In Vivo Response 353Jiunn H. LinIndex 383

“The ability to correlate in vitro and in vivo biomarker information in the process of drug discovery and development lies at the heart of translational research. The goal is to rapidly translate basic discoveries into clinical applications. This book provides state-of-the-art information on this exciting new research approach.”  (Doody’s, 8 February 2013)“The text is packed with interesting, comprehensive, and pertinent information, clearly presented with salient points reinforced by inclusion in text boxes . . . This is an admirable textbook for those dealing with drug discovery and development. I enjoyed reading through it and I would recommend it to anyone who has an interest, or is developing an interest, in the field of biomarkers and their, as yet, unfulfilled potential.”  (ISSX International Society for the Study of Xenobiotics, 1 December 2012)