1;Preface;5 2;Contents;10 3;List of Editors and Contributors;12 3.1;Editors;12 3.2;Contributors;12 4;1 Extrapolation of Preclinical Data into Clinical Reality - Translational Science;16 5;2 Smarter Candidate Selection - Utilizing Microdosing in Exploratory Clinical Studies;21 5.1;2.1 The Need for Exploratory Clinical Studies in the Successful Development of New Drugs;22 5.2;2.2 Concept of Microdosing;24 5.3;2.3 Applicability and Advantages of Microdosing;25 5.4;2.4 Prerequisites and Preparation for a Human Microdosing Study;27 5.5;2.5 Future of Microdosing;31 5.6;2.6 Conclusion;40 5.7;References;40 6;3 The Applications of Biomarkers in Early Clinical Drug Development to Improve Decision- Making Processes;42 6.1;3.1 Introduction;43 6.2;3.2 Definition and Classification;44 6.3;3.3 Why DoWe Need Biomarkers?;45 6.4;3.4 Validation;47 6.5;3.5 Regulatory Aspects;48 6.6;3.6 Examples for Using Biomarkers in Early Clinical Development;50 6.7;3.7 Conclusions;55 6.8;References;55 7;4 Using Exposure - Response and Biomarkers to Streamline Early Drug Development;59 7.1;Abbreviations;60 7.2;4.1 Guiding Principles;61 7.3;4.2 Role of Biomarkers in Drug Development;65 7.4;4.3 Case Example;70 7.5;4.4 Conclusions;73 7.6;References;74 8;5 Experiences with Dose Finding in Patients in Early Drug Development: The Use of Biomarkers in Early Decision Making;76 8.1;5.1 Introduction;77 8.2;5.2 Use of Biomarkers in Early Decision Making;78 8.3;5.3 Characterising the Dose Response;79 8.4;5.4 Applied Clinical Biomarkers: Two Examples from the Genitourinary Therapeutic Area;80 8.5;5.5 Summary;89 8.6;References;90 9;6 Genotype and Phenotype Relationship in Drug Metabolism;91 9.1;6.1 Introduction;92 9.2;6.2 Genotype-Phenotype Relations Leading to Dosage Recommendations;94 9.3;6.3 Genotype-Based Therapeutic Failure with 5- Hydroxytryptamine Type- 3 Receptor Antagonists;97 9.4;6.4 Individual Variations in CYP2C19-Metabolism of Proton Pump Inhibitors Determine Their Efficacy;98 9.5;6.5 Cyclophosphamide Kinetics Related to CYP2C19 Polymorphism;100 9.6;6.6 CYP2C9 Polymorphism;101 9.7;6.7 Estrogen Metabolism by CYP1A1 Variants;102 9.8;6.8 Genotype-Phenotype Relations in Drug Transporters;103 9.9;6.9 Some Concluding Statements Regarding Pharmacogenetics;106 9.10;References;107 10;7 Clinical Trials in Elderly Patients;111 10.1;7.1 Pharmacokinetics;112 10.2;7.2 Pharmacodynamics;115 10.3;7.3 Adverse Drug Reactions;116 10.4;7.4 Drug Interactions;117 10.5;7.5 Clinical Trial Design;117 10.6;7.6 Conclusions;118 10.7;References;119 11;8 Dose Finding in Pediatric Patients;120 11.1;8.1 Peculiarities of Childhood and Adolescence;121 11.2;8.2 Reasons for the Lack of Clinical Trials in Children;121 11.3;8.3 How to Select the Appropriate Dose?;122 11.4;8.4 Do We Need New Drugs?;124 11.5;8.5 The Role of Therapy Optimizing Studies in Pediatric Oncology;126 11.6;8.6 The Future;127 11.7;References;128 12;9 Integration of Pediatric Aspects into the General Drug Development Process;131 12.1;9.1 Clinical Drug Development is a Young Discipline;132 12.2;9.2 Off-Patent Use of Medicines in Children;132 12.3;9.3 US Pediatric Legislation and the Emerging EU Pediatric Regulation;133 12.4;9.4 Timing of Pediatric Development, Deferrals, andWaivers;135 12.5;9.5 Integrating Pediatric Aspects into the General Drug Development Process;136 12.6;9.6 Building up Pediatric Competency in Pharmaceutical Companies;138 12.7;9.7 Will the EU Draft Regulation Leading to More Pediatric Research in the Near Future?;138 12.8;9.8 Globalization of Clinical Research and Europe's Competitiveness;139 12.9;9.9 Conclusions;140 12.10;References;140 13;10 Current Stumbling Blocks in Oncology Drug Development;143 13.1;10.1 Introduction;144 13.2;10.2 Multitude of Targets: How to Select a Target?;144 13.3;10.3 Validation of a Target;145 13.4;10.4 Dose and Dose Regimen Findings with Molecularly Targeted Drugs;151 13.5;10.5 Appropriate Selection of Clinical Endpoints for Benefit Prediction;152 13.6;10.6 Integration of New Drugs