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.

Recommended use of antioxidant vitamins to treat varied medical maladies is based on the invalidated free radical theory. The continued non-acceptance of the null findings of over 500 clinical trials on vitamin and antioxidant supplements has no scientific basis or biochemical plausibility. The underlying principles of the free radical theory have been proven to have repeated unreliability. It fails to meet the requirements of the scientific method and lacks reproducibility. Yet, the multi-billion dollar antioxidant supplement industry continues to thrive and trumpet false claims for their potentially harmful products. No doubt, excessive intake of antioxidant vitamins results in increased risk of heart disease, cancer, strokes and overall mortality. A working knowledge of redox chemistry is essential to understanding the hundreds of failed trials testing the efficacy of antioxidant supplements and antioxidant vitamins. Normal redox homeostasis may be pathologically disturbed by overzealous use of antioxidants. My UTOPIA and ROS insufficiency theories present a new perspective more correctly informed by the most contemporaneous experimental findings and by the most reliable clinical trials and studies. In short, electronically modified oxygen derivatives (EMODs) are essential for human existence and protection. An EMOD insufficiency "allows" for the development of a multitude of disease entities, including infections, non-healing wounds, infertility, tumor development, arteriosclerotic blockages, and cancer growth and metastasis. There never has been a "war" between EMODs and antioxidants.