This volume is authored by esteemed experts in the field, and provides state-of-the art knowledge related to enzyme- and transporter-based DDIs that impact the absorption and disposition of drugs. It examines the types of DDIs, methodological approaches to evaluate and view DDIs mechanistically, bioinformatics, clinical and toxicological outcomes, and regulatory recommendations. As much as possible, the future challenges and opportunities that lie ahead are presented and discussed. Special emphases are placed on the quantitative assessment of the roles of different transporters, need for more specific probes and inhibitors, and recognition of extrahepatic eliminating organs. Future approaches should integrate transporters and enzymes to accelerate the development of physiological based-pharmacokinetic models (PBPK-DDI) and information related to inter-subject variability. In addition, the authors look beyond small molecules and consider DDIs involving biologic agents, such as therapeutic antibodies, that can bring about pharmacologically significant drug-cytokine or drug-endocrine interactions.
Author(s): Susan Kadlubar, Fred F. Kadlubar (auth.), K. Sandy Pang, A. David Rodrigues, Raimund M. Peter (eds.)
Edition: 1
Publisher: Springer-Verlag New York
Year: 2010
Language: English
Pages: 746
Tags: Pharmacology/Toxicology; Analytical Chemistry; Medicinal Chemistry
Front Matter....Pages i-xviii
Front Matter....Pages 1-1
Enzymatic Basis of Phase I and Phase II Drug Metabolism....Pages 3-25
Transporters: Importance in Drug Absorption, Distribution, and Removal....Pages 27-49
ADME Pharmacogenetics and Its Impact on Drug–Drug Interactions....Pages 51-74
Impact of Nuclear Receptors CAR, PXR, FXR, and VDR, and Their Ligands On Enzymes and Transporters....Pages 75-105
Impact of Physiological Determinants: Flow, Binding, Transporters and Enzymes on Organ and Total Body Clearances....Pages 107-147
Front Matter....Pages 149-149
In Silico Approaches to Predict DDIs....Pages 151-168
In Vitro Techniques to Study Drug–Drug Interactions of Drug Metabolism: Cytochrome P450....Pages 169-215
The In Vitro Characterization of Inhibitory Drug–Drug Interactions Involving UDP-Glucuronosyltransferase....Pages 217-236
In Vitro Techniques to Study Transporter-Based DDI....Pages 237-255
In Vitro Techniques to Study Drug–Drug Interactions Involving Transport: Caco-2 Model for Study of P-Glycoprotein and Other Transporters....Pages 257-282
Use of In Vivo Animal Models to Assess Drug–Drug Interactions....Pages 283-297
Extrapolation of In Vitro Metabolic and P-Glycoprotein-Mediated Transport Data to In Vivo by Modeling and Simulations....Pages 299-315
Translation of In Vitro Metabolic Data to Predict In Vivo Drug–Drug Interactions: IVIVE and Modeling and Simulations....Pages 317-341
Absorption Models to Examine Bioavailability and Drug–Drug Interactions in Humans....Pages 343-370
Management of Drug Interactions of New Drugs in Multicenter Trials Using the Metabolism and Transport Drug Interaction Database©....Pages 371-386
Web-Based Database as a Tool to Examine Drug–Drug Interactions Involving Transporters....Pages 387-412
Front Matter....Pages 413-413
Drug Disposition and Drug–Drug Interactions: Importance of First-Pass Metabolism in Gut and Liver....Pages 415-435
Transporter-Based Drug–Drug Interactions and Their Effect on Distribution Volumes....Pages 437-471
Inactivation of Human Cytochrome P450 Enzymes and Drug–Drug Interactions....Pages 473-495
Allosteric Enzyme- and Transporter-Based Interactions....Pages 497-515
Front Matter....Pages 413-413
The Impact and In Vitro to In Vivo Prediction of Transporter-Based Drug–Drug Interactions in Humans....Pages 517-553
Herbal Supplement-Based Interactions....Pages 555-584
Anticipating and Minimizing Drug Interactions in a Drug Discovery and Development Setting: An Industrial Perspective....Pages 585-624
Clinical Studies of Drug–Drug Interactions: Design and Interpretation....Pages 625-649
Toxicological Consequences of Drug–Drug Interactions....Pages 651-664
Front Matter....Pages 665-665
Complex Drug Interactions: Significance and Evaluation....Pages 667-692
Drug–Drug Interactions: Communicating Post-market Drug Safety Information in the USA....Pages 693-699
Drug–Drug Interactions: What Have We Learned and Where Are We Going?....Pages 701-722
Back Matter....Pages 723-746
