Drug-Drug Interactions in Pharmaceutical Development

Preface. Contributors. 1 In Vitro Evaluation of Metabolic Drug-Drug Interactions: Concepts and Practice (Albert P. Li). 1.1 Introduction. 1.2 Mechanisms of Adverse Drug-Drug Interactions. 1.3 Drug Metabolism. 1.4 CYP Isoforms. 1.5 Human In Vitro Experimental Systems for Drug Metabolism. 1.6 Mechanisms of Metabolic Drug-Drug Interactions. 1.7 Mechanism-Based Approach for Evaluation of Drug-Drug Interaction Potential. 1.8 Experimental Approaches for In Vitro Evaluation of Drug-Drug Interaction Potential. 1.9 Data Interpretation. 1.10 Conclusion. References. 2 In Vitro Approaches to Anticipating Clinical Drug Interactions (Laurie P. Volak, David J. Greenblatt, and Lisa L. von Moltke). 2.1 In Vitro Systems for Human CYP450 Metabolism. 2.2 Analysis of Data from In Vitro Systems. 2.3 Use of In Vitro Kinetic Data to Predict In Vivo Clearance. 2.4 Use of In Vitro Kinetic Data to Predict Drug-Drug Interactions. 2.5 Consideration of Non-CYP Enzymatic Systems. 2.6 Summary. 2.7 Acknowledgments. References. 3 Inhibition of Drug-Metabolizing Enzymes and Drug-Drug Interactions in Drug Discovery and Development (R. Scott Obach). 3.1 Introduction. 3.2 Laboratory Approaches Inhibiting Drug-Metabolizing Enzymes. 3.3 Selection of Substrates for Inhibition Experiments in Drug Metabolism. 3.4 Inhibition of Drug-Metabolizing Enzymes in Drug Discovery and Development. 3.5 Summary. References. 4 Mechanism-Based CYP Inhibition: Enzyme Kinetics, Assays, and Prediction of Human Drug-Drug Interactions (Magang Shou). 4.1 Kinetic Model for Mechanism-Based Inhibition. 4.2 Methodological Measurements of Kinetic Parameters. 4.3 Incubation. 4.4 Prediction of Human DDIs from In Vitro MBI Data. 4.5 Acknowledgments. References. 5 Genomic Approaches To Drug-Drug Interactions (Yi Yang and Jeffrey F. Waring). 5.1 Introduction. 5.2 DNA Microarrays. 5.3 Genomic Application Toward the Prediction of DDIs. 5.4 Genomics Approach to Decipher the Molecular Basis of DDI: Nuclear Receptors. 5.5 Genomic Approaches to Address the Genetic Variability in DDIs. 5.6 Conclusion. References. 6 Transporters and Drug Interactions (Yoshihisa Shitara, Toshiharu Horie, and Yuichi Sugiyama) 6.1 Introduction. 6.2 Interactions Involving Liver Transporters. 6.3 Interactions in Intestine Transporters. 6.4 Drug Toxicity Involving Drug Transporters. 6.5 Drugs that Affect the Expression or Localization of Transporters. 6.6 Conclusion. References. 7 Transporter-Mediated Drug Interactions: Molecular Mechanisms and Clinical Implications (Jiunn H. Lin). 7.1 Introduction. 7.2 Tissue Distribution and Cellular Location of Transporters. 7.3 Molecular Mechanisms for Transporter Inhibition and Induction. 7.4 Drug Interactions Caused by Transporter Inhibition and Induction. 7.5 Clinical Significance of Transporter-Mediated Drug Interactions. 7.6 Conclusion. References. 8 Recent Case Studies of Clinically Significant Drug-Drug Interactions and the Limits of In Vitro Prediction Methodology (René H. Levy, Isabelle Ragueneau-Majlessi, and Carol Collins). 8.1 Introduction. 8.2 Case Studies. References. 9 U.S. Regulatory Perspective: Drug-Drug Interactions (John Strong and Shiew-Mei Huang). 9.1 Introduction. 9.2 An Integrated Approach. 9.3 Methods for Evaluating Metabolic Clearance In Vitro. 9.4 In Vivo Approaches. 9.5 Clinical Cases. 9.6 Regulatory Considerations. 9.7 Labeling. 9.8 Summary. References. 10 Herbal Drug Interactions--A Canadian Perspective (Brian C. Foster) 10.1 Introduction. 10.2 Interaction Risk Determination. 10.3 NHP Products. 10.4 Disposition. 10.5 PD and PK interactions. 10.6 Action. References. Index. Wiley Series in Drug Discovery and Development.