Predictive Approaches in Drug Discovery and Develo pment: Biomarkers and In Vitro / In Vivo Correlati ons

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 xi ACKNOWLEDGMENTS xiii CONTRIBUTORS xv PART I BIOMARKERS IN DRUG DISCOVERY 1 1 The Importance of Biomarkers in Translational Medicine 3 Joseph C. Fleishaker 2 Validation of Biochemical Biomarker Assays used in Drug Discovery and Development: A Review of Challenges and Solutions 23 Gabriella Szekely-Klepser and Scott Fountain 3 Proteomic Methods to Develop Protein Biomarkers 49 Ruth A. VanBogelen and Diane Alessi 4 Overview of Metabolomics Basics 79 Qiuwei Xu and William H. Schaefer PART II CLINICAL APPLICATION OF BIOMARKERS 139 5 Vascular Biomarkers and Imaging Studies 141 Karin Potthoff, Ulrike Fiedler, and Joachim Drevs 6 Cardiovascular Biomarkers as Examples of Success and Failure in Predicting Safety in Humans 163 Simon Authier, Michael K. Pugsley, Eric Troncy, and Michael J. Curtis 7 The Use of Molecular Imaging for Receptor Occupancy Decision Making in Drug Development 189 Ralph Paul Maguire 8 Biosensors for Clinical Biomarkers 203 Sara Tombelli and Marco Mascini PART III REGULATORY PERSPECTIVES 229 9 Regulatory Perspectives on Biomarker Development 231 Rajanikanth Madabushi, Lawrence Lesko, and Janet Woodcock 10 Perspectives from the European Regulatory Authorities 255 Ian Hudson 11 Use of Biomarker in Drug Development-Japanese Perspectives 269 Yoshiaki Uyama, Akihiro Ishiguro, Harumasa Nakamura,and Satoshi Toyoshima PART IV PREDICTING IN VIVO 289 12 In Vitro - In Vivo Correlations of Hepatic Drug Clearance 291 R. Scott Obach 13 The Potential of In Silico and In Vitro Approaches to Predict In Vivo Drug-Drug Interactions and ADMET/TOX Properties 307 Kenneth Bachmann and Sean Ekins 14 In Vitro - In Vivo Correlations in Drug Discovery and Development: Concepts and Applications in Toxicology 331 Rex Denton, Kimberly Brannen, and Bruce D. Car 15 Assessing the Potential for Induction of Cytochrome P450 Enzymes and Predicting the In Vivo Response 353 Jiunn H. Lin INDEX 383