Authored by renowned leaders in the field, this comprehensive volume covers all aspects of drug-drug interactions, including preclinical, clinical, toxicological, and regulatory perspectives.
Thoroughly updated, this second edition reflects the significant advances and includes extensive new material on:
- key interplay between transporters and enzymes in drug metabolism and drug interactions
- the integral role of pharmacogenetics in metabolism-based drug-drug interactions
- in vivo – in vitro correlations (reversible, mechanism-based inhibition, induction)
- in silico approaches enabling structure-activity and structure-function studies
- high-throughput screening and GLP methods for evaluating drug interactions in vitro
- the use of transgenic animal models to evaluate drug interactions
Providing helpful case examples and computer-aided modeling, Drug-Drug Interactions is filled with over 200 invaluable tables, equations, and figures to clarify key concepts, and incorporates critical new updated information.
Table of Contents
Introducing Pharmacokinetics and Pharmacodynamic Concepts. In Vitro Enzyme Kinetics Applied to Drug-Metabolizing Enzymes. Human Cytochromes P450 and Their Role in Metabolism-Based Drug-Drug Interactions. UDP-Glucuronosyltransferases. Drug-Drug Interactions Involving the Membrane Transport Process. In Vitro Models for Studying Induction of Cytochrome P450 Enzymes. In Vitro Approaches for Studying the Inhibition of Drug-Metabolizing Enzymes and Identifying the Drug-Metabolizing Enzymes Responsible for the Metabolism of Drugs (Reaction Phenotyping) with Emphasis on Cytochrome P450. The Role of P-Glycoprotein in Drug Disposition: Significance to Drug Development. Cytochrome P450 Protein Modeling and Ligand Docking. The Role of the Gut Mucosa in Metabolically Based Drug-Drug Interactions. Mechanism-Based Inhibition of Human Cytochromes P450: In Vitro Kinetics and In Vitro-In Vivo Correlations. Transporter-mediated Drug Interactions: Molecular Mechanisms and Clinical Implications. Metabolism & Transport Drug Interaction Database: a web-based research and analysis tool. In Vivo Probes for Studying Induction and Inhibition of Cytochrome P450 Enzymes in Humans. Drug-Drug Interactions: Clinical Perspective. An Integrated Approach to Assessing Drug-Drug Interactions: A Regulatory Perspective. Drug-Drug Interactions: Toxicological Perspectives. Drug-Drug Interactions: Marketing Perspectives.
A. DAVID RODRIGUES is Executive Director, Metabolism and Pharmacokinetics, Bristol-Myers Squibb, Pharmaceutical Research Institute, Princeton, NJ, and received his Ph.D. in Biochemistry from the University of Surrey, Guildford, UK. Dr. Rodrigues is a member of the American Association of Pharmaceutical Scientists and is presently serving on the Scientific Affairs Committee of the International Society for the Study of Xenobiotics. He has authored more than 75 peer-reviewed articles and over one dozen book chapters, and sits on the Editorial Board of three journals (Drug Metabolism and Disposition, Drug Metabolism Letters, and Current Drug Metabolism).