Introduction-Since their initial discovery in 1989, grapefruit juice-drug interactions have received extensive interest from the scientific, medical, regulatory, and lay communities. Although knowledge regarding the effects of grapefruit juice on drug disposition continues to expand, the list of drugs studied in the clinical setting remains relatively limited.Areas covered-This article reviews the in vitro effects of grapefruit juice and its constituents on the activity of cytochrome P450 enzymes, organic anion-transporting polypeptides, Pglycoprotein, esterases and sulfotransferases. The translational applicability of the in vitro findings to the clinical setting is discussed for each drug metabolizing enzyme and transporter. Reported area under the plasma concentration-time curve ratios for available grapefruit juice-drug interaction studies are also provided. Relevant investigations were identified by searching the Pubmed electronic database from 1989 to 2010.Expert opinion-Grapefruit juice increases the bioavailability of some orally-administered drugs that are metabolized by CYP3A and normally undergo extensive presystemic extraction. In addition, grapefruit juice can decrease the oral absorption of a few drugs that rely on organic anion-transporting polypeptides in the gastrointestinal tract for their uptake. The number of drugs shown to interact with grapefruit juice in vitro is far greater than the number of clinically relevant grapefruit juice-drug interactions. For the majority of patients, complete avoidance of grapefruit juice is unwarranted.

Fermentation properties of oligosaccharides derived from orange peel pectin were assessed in mixed fecal bacterial culture. The orange peel oligosaccharide fraction contained glucose in addition to rhamnogalacturonan and xylogalacturonan pectic oligosaccharides. Twenty-four-hour, temperature-and pH-controlled, stirred anaerobic fecal batch cultures were used to determine the effects that oligosaccharides derived from orange products had on the composition of the fecal microbiota. The effects were measured through fluorescent in situ hybridization to determine changes in bacterial populations, fermentation end products were analyzed by high-performance liquid chromatography to assess short-chain fatty acid concentrations, and subsequently, a prebiotic index (PI) was determined. Pectic oligosaccharides (POS) were able to increase the bifidobacterial and Eubacterium rectale numbers, albeit resulting in a lower prebiotic index than that from fructo-oligosaccharide metabolism. Orange albedo maintained the growth of most bacterial populations and gave a PI similar to that of soluble starch. Fermentation of POS resulted in an increase in the Eubacterium rectale numbers and concomitantly increased butyrate production. In conclusion, this study has shown that POS can have a beneficial effect on the fecal microflora; however, a classical prebiotic effect was not found. An increase in the Eubacterium rectale population was found, and butyrate levels increased, which is of potential benefit to the host.The concept of modulating gut health through diet is not new and dates back to at least the beginning of the 20th century. However, it is only recently that sound scientific rationales have been proposed and investigated. Three microflora modulation tools have emerged (40): the addition of exogenous living microorganisms to foods (i.e., probiotics), the selective stimulation of the growth and activity of beneficial microorganisms indigenous to the gut (i.e., prebiotics), and a combination of both approaches (i.e., synbiotics). All three approaches attempt to increase the numbers of bacteria seen as positive for human gastrointestinal health, usually the lactobacilli and bifidobacteria. Prebiotics have been defined as "non-digestible food ingredients that selectively stimulate a limited number of bacteria in the colon, to improve host health" (12). Bifidobacteria and lactobacilli are known to directly inhibit the growth of pathogenic bacteria, such as certain species of clostridia (e.g., Clostridium difficile and C. perfringens) and pathogenic Enterobacteriaceae, through the production of short-chain fatty acids, lowering of colonic pH, production of antimicrobial compounds, and/or competition for growth substrates and adhesion sites (13,23,27). The bifidogenic nature of a range of prebiotics has now been confirmed in vivo in human feeding studies (11,37). These prebiotics include inulin, fructo-oligosaccharides (FOS), galacto-oligosaccharides, and lactulose (42,43,25,44).The aim of the present work was to assess the prebiotic...

Furanocoumarins are the active ingredients in GFJ responsible for enhancing the systemic exposure of felodipine and probably other CYP3A4 substrates that undergo extensive intestinal first-pass metabolism.