Predictive Approaches in Drug Discovery and Development

PREFACE xi
ACKNOWLEDGMENTS xiii
CONTRIBUTORS xv
PART I BIOMARKERS IN DRUG DISCOVERY 1
1 The Importance of Biomarkers in Translational Medicine3
Joseph C. Fleishaker
2 Validation of Biochemical Biomarker Assays used in DrugDiscovery and Development: A Review of Challenges and Solutions23
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 andFailure in Predicting Safety in Humans 163
Simon Authier, Michael K. Pugsley, Eric Troncy, and MichaelJ. Curtis
7 The Use of Molecular Imaging for Receptor OccupancyDecision 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 JanetWoodcock
10 Perspectives from the European Regulatory Authorities255
Ian Hudson
11 Use of Biomarker in Drug Development--Japanese
Perspectives 269 Yoshiaki Uyama, Akihiro Ishiguro, HarumasaNakamura,and Satoshi Toyoshima
PART IV PREDICTING IN VIVO 289
12 In Vitro-In Vivo Correlations ofHepatic Drug Clearance 291
R. Scott Obach
13 The Potential of In Silico and In VitroApproaches to Predict In Vivo Drug-Drug Interactionsand ADMET/TOX Properties 307
Kenneth Bachmann and Sean Ekins
14 In Vitro-In Vivo Correlations in DrugDiscovery and Development: Concepts and Applications in Toxicology331
Rex Denton, Kimberly Brannen, and Bruce D. Car
15 Assessing the Potential for Induction of CytochromeP450 Enzymes and Predicting the In Vivo Response353
Jiunn H. Lin
INDEX 383