Iwao Kazunari, Kawai Rushiana Tokie, Oda Masako, Saitoh Hiroshi
Department of Pharmacy, Health Sciences University of Hokkaido Hospital.
Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido.
Biol Pharm Bull. 2017;40(9):1566-1571. doi: 10.1248/bpb.b17-00149.
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.
本研究的目的是使用一种简单的离心方法评估各种药物与日本流行的健康食品青汁之间的相互作用。将药物溶液和青汁悬浮液混合后轻轻摇晃并离心。然后通过高效液相色谱法测定上清液中的药物浓度。与青汁混合后,模型化合物罗丹明123(Rho-123)在上清液中的浓度显著降低,表明Rho-123与青汁的不溶性成分广泛结合。当与青汁一起注入大鼠小肠肠袢时,血浆Rho-123浓度比单独给药时小得多。这一结果强烈表明,体外观察到的强相互作用在调节吸收中得到了很好的体现。在所测试的七种药物中,氯丙嗪和丙咪嗪对青汁的结合特性与Rho-123相似或更强。当青汁沉淀物重新悬浮时,Rho-123和丙咪嗪都有一小部分释放出来,因此它们与青汁的结合被认为是紧密的。与氯丙嗪和丙咪嗪相比,地尔硫卓、非索非那定、格列本脲、二甲双胍和诺氟沙星与青汁的结合要弱得多或几乎可以忽略不计。目前的结果表明,青汁可以通过在小肠中的紧密结合降低某些临床相关药物的肠道吸收,并且目前的离心方法可用于预测药物与青汁之间的体内相互作用。