Predictive Approaches in Drug Discovery and Development (eBook)

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 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 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

"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)