Description
Springer Enzyme- And Transporter-Based Drug-Drug Interactions Progress And Future Challenges 2010 Edition by K. Sandy Pang A. David Rodrigues Raimund M. Peter
Germination of the thought of "Enzymatic- and Transporter-Based Drug-Drug Interactions: Progress and Future Challenges" Proceedings came about as part of the annual meeting of The American Association of Pharmaceutical Scientists (AAPS) that was held in San Diego in November of 2007. The attendance of workshop by more than 250 pharmaceutical scientists reflected the increased interest in the area of drug-drug interactions (DDIs) the greater focus of PhRMA academia and regulatory agencies and the rapid pace of growth in knowledge. One of the aims of the workshop was to address the progress made in quantitatively predicting enzyme- and transporter-based DDIs as well as highlighted areas where such predictions are poor or areas that remain challenging for the future. Because of the serious clinical implications initiatives have arisen from the FDA (http://www.fda.gov/cber/gdlns/interactstud.htm) to highlight the importance of enzyme- and transporter-based DDIs. During the past ten to fifteen years we have come to realize that transporters in addition to enzymes play a vital role in drug elimination. Such insight has been possible because of the continued growth in PK-ADME (pharmacokinetics-absorption-distribution-metabolism-excretion) knowledge fueled by further advances in molecular biology greater availability of human tissues and the development of additional and sophisticated model systems and sensitive assay methods for studying drug metabolism and transport in vitro and in vivo. This has sparked an in-depth probing into mechanisms surrounding DDIs resulting from ligand-induced changes in nuclear receptors as well as alterations in transporter and enzyme expression and function. Despite such advances the in vitro and in vivo study of drug interactions and the integration of various data sets remain challenging. Therefore it has become apparent that a proceeding that serves to encapsulate current strategies approaches methods and applications is necessary. As Editors we have assembled a number of opinion leaders and asked them to contribute chapters surrounding these issues. Many of these are the original Workshop speakers whereas others had been selected specially to contribute on topics related to basic and applied information that had not been covered in other reference texts on DDI. The resulting tome entitled Enzyme- and Transporter-Based Drug Interactions: Progress and Future Challenges comprises of four sections. Twenty-eight chapters covering various topics and perspectives related to the subject of metabolic and transporter-based drug-drug interactions are presented. Table of contents : Section I: Determinants of Drug ADME1. Enzymatic Basis Of Phase I And Phase II Drug Metabolism2. Transporters: Importance In Drug Absorption Distribution And Elimination3. ADME Pharmacogenetics and Its Impact on Drug-Drug Interactions4. Impact Of Nuclear Receptors CAR PXR FXR And VDR And Their Ligands On Enzymes And Transporters5. Impact of Physiological Determinants: Flow Binding Transporters And Enzymes On Organ and Total Body ClearancesSection II: Methods For The Study Of Drug-Drug Interactions6. In Silico Approaches to Predict Drug-Drug Interactions7. In Vitro Techniques To Study Drug-Drug Interactions Of Drug Metabolism: Cytochrome P4508. In Vitro Characterization Of Inhibitory Drug-Drug Interactions Involving UDP-Glucuronosyltransferase9. In Vitro Techniques To Study Transporter-Based Drug-Drug Interactions10. In Vitro Techniques To Study Drug-Drug Interactions Involving Transport: Caco-2 Model For Study Of P-Glycoprotein And Other Transporters11. Use Of In Vivo Animal Models To Assess Drug-Drug Interactions12. Extrapolation of In Vitro Metabolic and P-Glycoprotein-mediated Transport Data To In Vivo By Modeling and Simulations13. Translation Of In Vitro Metabolic Data To Predict In Vivo Drug-Drug Interactions: IVIVE And Modeling And Simulations14. Absorption Models To Examine Bioavailability And DDI's In Humans15. Management Of Drug Interactions Of New Drugs In Multicenter Trials Using The Metabolism & Transport Drug Interaction Database (c) 16. Web-Based Database As A Tool To Examine Drug-Drug Interactions Involving Transporters Section III: Impact Of Drug-Drug Interactions17. Drug Disposition And Drug-Drug Interactions: Importance Of First-Pass Metabolism In Gut And Liver18. Transporter Based Drug-Drug Interactions And Their Effect On Distribution Volumes19. Inactivation Of Human Cytochrome P450Enzymes And Drug-Drug Interactions20. Allosteric Enzyme And Transporter Based Interactions21. Interplay Of Transporter-Drug Interaction: Complications Of Both Inhibitory And Inductive Events In Drug-Drug Interaction22. Herbal Supplement-Based Interactions23. Anticipating And Minimizing Drug Interactions In A Drug Discovery And Development Setting: Industrial Perspective24. Clinical Studies Of Drug-Drug Interactions: Design And Interpretation25. Toxicological Consequences Of Drug Drug InteractionsSection IV: Regulatory Aspects And Future Developments Involving DDI26. Complex Drug Interactions: Significance And Evaluation27. DDI: Labeling And Marketing Perspectives28. Drug-Drug Interactions: What Have We Learnt And Where Are We Going?