Practical Utility of Biomarkers in Drug Discovery and Development covers all aspects of biomarker research applied to drug discovery and development and contains state-of-the-art appraisals on the practical utility of genomic, biochemical, and protein biomarkers.  Case histories and lessons from successful and unsuccessful applications of biomarkers are included along with key chapters on GLP validation, safety biomarkers and proteomics biomarkers.  Regulatory agency perspectives and initiatives both in the US and internationally are also discussed.

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 ofChallenges 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 DevelopmentJapanese Perspectives 269
Yoshiaki Uyama, Akihiro Ishiguro, Harumasa Nakamura, and Satoshi Toyoshima

Part IV Predicting in Vivo 289

12 In VitroIn Vivo Correlations of Hepatic Drug Clearance 291
R. Scott Obach

13 The Potential of In Silico and In Vitro Approaches to Predict In Vivo DrugDrug Interactions and ADMET/TOX Properties 307
Kenneth Bachmann and Sean Ekins

14 In VitroIn Vivo Correlations in Drug Discovery and Development: Concepts and Applications inToxicology 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