This state-of-the-art reference provides comprehensive coverage of the preclinical, clinical, toxicological, regulatory, and marketing perspectives of metabolism-based drug–drug interactions—relating pharmacokinetic concepts to Michaelis-Menten kinetics.

Uses helpful examples, representative enzyme systems, and computer-aided modeling to clarify key concepts! With contributions by world-renowned experts in the field, Drug-Drug Interactions discusses:

• kinetics-based in vitro–in vivo correlations
• modern methods for the development of a metabolic drug interaction (MDI) database
• the role of cytochromes P450, UDP-glucuronosyltransferases, and transporters in drug–drug interactions
• "tracking" the absorption, distribution, metabolism, and elimination of new drugs from biological systems
• enzyme inhibition and induction
• and much more!

Offering more than 2000 contemporary references and nearly 200 useful tables, equations, drawings, and photographs, Drug-Drug Interactions is an invaluable, must-read source for clinical, industrial, and research pharmacologists and pharmacists; medicinal and pharmaceutical chemists and biochemists; molecular biologists; toxicologists and molecular toxicologists; and upper-level undergraduate and graduate students in these disciplines.

Contents

1. Introducing Pharmacokinetics and Pharmacodynamic Concepts
2. In Vitro Enzyme Kinetics Applied to Drug-Metabolizing Enzymes
3. Human Cytochromes P450 and Their Role in Metabolism-Based Drug–Drug Interactions
4. Review of Human UDP-Glucuronosyltransferases and Their Role in Drug–Drug Interactions
5. Drug–Drug Interactions Involving the Membrane Transport Process
6. In Vitro Models for Studying Induction of Cytochrome P450 Enzymes
7. In Vitro Approaches for Studying the Inhibition of Drug-Metabolizing Enzymes and Identifying the Drug-Metabolizing Enzymes Responsible for the Metabolism of Drugs
8. The Role of P-Glycoprotein in Drug Disposition: Significance to Drug Development
9. The Role of the Gut Mucosa in Metabolically Based Drug–Drug Interactions
10. Mechanism-Based Inhibition of Human Cytochromes P450: In Vitro Kinetics and In Vitro–In Vivo Correlations
11. Prediction of Metabolic Drug Interactions: Quantitative or Qualitative?
12. In Vivo Probes for Studying Induction and Inhibition of Cytochrome P450 Enzymes in Humans
13. Molecular Modeling Approaches to Predict Drug Metabolism and Toxicity
14. Development of a Metabolic Drug Interaction Database at the University of Washington
15. Drug–Drug Interactions: Clinical Perspective
16. Drug–Drug Interactions: Toxicological Perspectives
17. An Integrated Approach to Assessing Drug–Drug Interactions: A Regulatory Perspective
18. Drug–Drug Interactions: Marketing Perspectives

Index

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