Predictive Approaches in Drug Discovery and Development: Biomarkers and In Vitro / In Vivo Correlations

Comprehensive coverage of biomarker research applied to drugdiscovery and development

Two key factors have emerged in the race to discover approvablenew drugs faster and with fewer resources: biomarkers and invitro/in vivo correlations (IVIVC). Predictive Approaches in DrugDiscovery and Development: Biomarkers and In Vitro/In VivoCorrelations provides comprehensive coverage of how these factorsare enhancing the drug pipeline and accelerating development.

An invaluable resource, the book presents essential informationon the importance of biomarkers in translational medicine, theclinical applications of biomarkers, relevant regulatoryperspectives, and the potential of in vivo research. With eachchapter written by one or more expert authors from the global frontlines of the pharmaceutical industry and regulatory agencies, thebook also incorporates academic research that unites these twofields and describes their applications, from technical labexperiments to strategic management.

Covering many aspects of biomarker research as applied to drugdiscovery and development, the book brings togetherstate–of–the–art appraisals of the practical utility of "–omics",biochemical, and protein biomarkers with case histories and lessonsfrom successful and unsuccessful real–world applications.Regulatory agency perspectives and initiatives in the United Statesand around the world are also discussed, as are GLP validation and,safety biomarkers, and proteomic biomarkers.

Biomarkers and IVIVC present unique opportunities foridentifying more robust clinical candidates and selecting leadsmore intelligently, making Predictive Approaches in Drug Discoveryand Development a must–have for researchers and professionals inthe pharmaceutical and biotechnology industries, as well as for usein advanced graduate and undergraduate courses.

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

J. Andrew Williams, PHD, is Director of Translational Oncologyat Pfizer Oncology.

Richard Lalonde, PharmD, is Vice President and Global Head ofClinical Pharmacology at Pfizer.

Jeffrey Koup, PharmD, is a consultant for PKPD modeling and theowner of Lakeside PKPD, LLC.

David D. Christ, PHD, is a consultant with SNC Partners LLC.

The ability to correlate in vitro and in vivo biomarkerinformation in the process of drug discovery and development liesat the heart of translational research. The goal is to rapidlytranslate basic discoveries into clinical applications. This bookprovides state–of–the–art information on this exciting new researchapproach.   (Doody s, 8 February 2013)

The text is packed with interesting, comprehensive, andpertinent information, clearly presented with salient pointsreinforced by inclusion in text boxes . . . This is an admirabletextbook for those dealing with drug discovery and development. Ienjoyed reading through it and I would recommend it to anyone whohas an interest, or is developing an interest, in the field ofbiomarkers and their, as yet, unfulfilled potential.  (ISSX International Society for the Study of Xenobiotics, 1December 2012)