In this study, as an approach to possible pharmacokinetic interactions between antidiabetic agents and health foods, we investigated the binding of metformin and glibenclamide to aojiru, kurosu, and blueberry extract using a dialysis method. The permeation of metformin from the inner to the outer side of the dialysis tube during 90 min was not altered in the presence of aojiru or kurosu, and slightly decreased by 20% compared with the control in the presence of blueberry extract, indicating that the interactions between metformin and these three health foods are limited. On the other hand, when these three health foods were added to inner medium together with glibenclamide, they significantly lowered the outer glibenclamide concentrations. The magnitude of the decrease in the outer glibenclamide concentrations was the most extensive in the presence of kurosu (60%), followed by aojiru (36%) and blueberry extract (45%). The present results suggest that metformin and glibenclamide interact differently with aojiru, kurosu, and blueberry extract and that these three health foods might modulate the absorption of glibenclamide in vivo.

The objective of this study was to evaluate the interactions between various drugs and aojiru (green juice), a popular health food in Japan, using a simple centrifugation method. The mixture of drug solution and aojiru suspension was gently shaken and centrifuged. The drug concentration in the supernatant fluid was then determined by HPLC. The concentration of rhodamine 123 (Rho-123), a model compound, in the supernatant fluid significantly decreased after mixing with aojiru, indicating extensive binding of Rho-123 to the insoluble components of aojiru. When administered into rat small intestinal loops together with aojiru, the plasma Rho-123 concentrations became much smaller than those when administered alone. This result strongly suggested that a strong interaction observed in vitro was well reflected in modulated absorption. Among seven drugs tested, chlorpromazine and imipramine exerted binding properties to aojiru similar to or greater than Rho-123. As a small part of both Rho-123 and imipramine was released when the aojiru precipitate was resuspended, their binding to aojiru was considered to be tight. The binding of diltiazem, fexofenadine, glibenclamide, metformin, and norfloxacin to aojiru was much weaker or almost negligible compared with that of chlorpromazine and imipramine. The present results suggest that aojiru can decrease the intestinal absorption of some clinically relevant drugs through tight binding in the small intestine and that the present centrifugation method is useful for predicting in vivo interactions between drugs and aojiru.Key words aojiru; drug interaction; centrifugation method; tricyclic cationic drug; intestinal absorption In Japan, with the recent increase in interest regarding health control, the use of health foods and dietary supplements has grown in getting popularity with patients as well as among the healthy population. However, limited information about the efficacy and safety of health foods and dietary supplements has been provided to consumers. Under such circumstances, unfavorable effects from the consumption of health foods and dietary supplements have been noted. 1,2) Moreover, undesirable pharmacokinetic or pharmacodynamic interactions have been reported with various drugs. [3][4][5][6][7] We also demonstrated that kurosu (Japanese unpolished rice vinegar) is capable of modulating the intestinal absorption of P-glycoprotein (P-gp) substrates. 8) Accordingly, further accumulation of information about clinically relevant interactions between drugs and various kinds of health foods is required.We previously reported the results of a questionnaire survey about the use of health foods among diabetic outpatients at the Health Sciences University of Hokkaido Hospital. 9)The most frequently consumed health food was aojiru (green juice). Aojiru, one of the most popular health foods in Japan, is made from green vegetables such as kale, ashitaba, mulberry leaf and barley grass and considered useful as a dietary fibers supplement.10,11) However, aojiru products contain larg...