Ni Hao, Matsumoto Takashi, Watanabe Junko, Makino Toshiaki
Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
Tsumura Kampo Research Laboratories, Kampo Research & Development Division, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Evid Based Complement Alternat Med. 2018 Oct 1;2018:4259603. doi: 10.1155/2018/4259603. eCollection 2018.
Recently, the use of herbal medicines has become popular, and information on drug interactions between herbal medicines and chemical drugs is needed in clinics. In Japan, the number of patients taking Japanese traditional Kampo medicines has been increasing, and the proper drug information about herb-drug interaction is highly demanded. The most established herb-drug interaction is the case of grapefruit juice (GFJ) the inhibition on CYP3A4 expressed in the small intestine. In the present study, we compared the inhibitory titer on CYP3A4 between the target Kampo products and GFJ used as positive control. We evaluated the inhibitory effects of GFJ and three extracts of Kampo formulas frequently used in gynecological clinics on CYP3A4 and calculated the related titer of one-time dosage of Kampo formulas to GFJ in order to predict its effect on clinics. Although the extracts of these three Kampo formulas and the most of crude drug components in the formulas exhibited the inhibitory effects on CYP3A4 in some levels, the possibilities of tokishakuyakusan and keishibukuryogan to cause drug interaction can be quite low; however, it is possible that the excessive dosage of kamishoyosan may cause drug interaction with the substrate of CYP3A4 in clinics.
近年来，草药的使用日益普遍，临床上需要有关草药与化学药物之间药物相互作用的信息。在日本，服用日本传统汉方药的患者数量一直在增加，因此对草药-药物相互作用的适当药物信息有很高的需求。最典型的草药-药物相互作用案例是葡萄柚汁（GFJ）对小肠中表达的CYP3A4的抑制作用。在本研究中，我们比较了目标汉方产品与用作阳性对照的GFJ对CYP3A4的抑制效价。我们评估了GFJ和妇科诊所常用的三种汉方配方提取物对CYP3A4的抑制作用，并计算了汉方配方单次剂量与GFJ的相关效价，以预测其对临床的影响。尽管这三种汉方配方的提取物以及配方中的大多数生药成分在一定程度上对CYP3A4表现出抑制作用，但芍药甘草散和桂枝茯苓丸引起药物相互作用的可能性可能相当低；然而，在临床上，加味逍遥散过量服用可能会与CYP3A4的底物发生药物相互作用。
