Springer Enzyme- and Transporter-Based Drug-Drug Interactions: Progress and Future Challenges

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. From the Back Cover 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. About the Author K. Sandy Pang Ph.D. is Professor of Pharmacy and Pharmacology, Faculties of Pharmacy and Medicine at the University of Toronto. She received her B.S