Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin
Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin
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DOI：
10.1007/s12272-014-0510-6
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发表时间：
2015-05-01
影响因子：
6.7
通讯作者：
Song, Im-Sook
中科院分区：
文献类型：
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作者：
Kwon, Mihwa;Choi, Young A.;Song, Im-Sook
小檗碱是草药黄连的主要活性成分，据报道具有降血糖和胰岛素增敏作用，因此可以与二甲双胍联合治疗。因此，我们评估了小檗碱和二甲双胍之间潜在的药物相互作用。我们研究了小檗碱对过表达有机阳离子转运蛋白 (OCT) 1 和 2 的 HEK293 细胞中二甲双胍摄取的体外抑制效力。为了研究小檗碱对 OCT1 和 OCT2 的抑制作用是否会改变二甲双胍体内的药代动力学，我们测量了单次静脉注射 2 mg/kg 二甲双胍剂量时联合给药小檗碱对二甲双胍药代动力学的影响和10毫克/千克小檗碱。在HEK293细胞中，小檗碱以浓度依赖性方式抑制OCT1和OCT2介导的二甲双胍摄取，OCT1和OCT2的IC50值分别为7.28和11.3μM。联合给予小檗碱可增加二甲双胍的初始血浆浓度和 AUC，并降低二甲双胍的全身清除率和分布容积，表明小檗碱抑制二甲双胍的处置，而二甲双胍的处置由 OCT1 和 OCT2 控制。小檗碱抑制 OCT1 和 OCT2 的转运活性，并在大鼠体内与二甲双胍显示出显着的潜在药物相互作用。
Berberine, the main active component of the herbal medicine Rhizoma Coptidis, has been reported to have hypoglycemic and insulin-sensitizing effects and, therefore, could be combined with metformin therapy. Thus, we assessed the potential drug-drug interactions between berberine and metformin. We investigated the in vitro inhibitory potency of berberine on metformin uptake in HEK293 cells overexpressing organic cation transporter (OCT) 1 and 2. To investigate whether this inhibitory effect of berberine on OCT1 and OCT2 could change the pharmacokinetics of metformin in vivo, we measured the effect of berberine co-administration on the pharmacokinetics of metformin at a single intravenous dose of 2 mg/kg metformin and 10 mg/kg berberine. In HEK293 cells, berberine inhibited OCT1- and OCT2-mediated metformin uptake in a concentration dependent manner and IC50 values for OCT1 and OCT2 were 7.28 and 11.3 mu M, respectively. Co-administration of berberine increased the initial plasma concentration and AUC of metformin and decreased systemic clearance and volume of distribution of metformin in rats, suggesting that berberine inhibited disposition of metformin, which is governed by OCT1 and OCT2. Berberine inhibited the transport activity of OCT1 and OCT2 and showed significant potential drug-drug interactions with metformin in in vivo rats.