Laboratory of Clinical Pharmacodynamics, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
Drug Metab Pharmacokinet. 2011;26(5):486-93. doi: 10.2133/dmpk.dmpk-11-rg-020. Epub 2011 Jun 21.
Several kinds of food have been shown to influence the absorption and metabolism of drugs, although there is little information about their effect on the renal excretion of drugs. In this study, we performed uptake experiments using Xenopus laevis oocytes to assess the inhibitory effects of chlorogenic acid, caffeic acid and quinic acid, which are contained in coffee, fruits and vegetables, on human organic anion transporters hOAT1 and hOAT3; these transporters mediate renal tubular uptake of anionic drugs from blood. Injection of hOAT1 and hOAT3 cRNA into oocytes stimulated uptake of typical substrates of hOAT1 and hOAT3 (p-aminohippurate and estrone sulfate, respectively); among the three compounds tested, caffeic acid most strongly inhibited these transporters. The apparent 50% inhibitory concentrations of caffeic acid were estimated to be 16.6 µM for hOAT1 and 5.4 µM for hOAT3. Eadie-Hofstee plot analysis showed that caffeic acid inhibited both transporters in a competitive manner. In addition to the transport of p-aminohippurate and estrone sulfate, that of antifolates and antivirals was inhibited by caffeic acid. These findings show that caffeic acid has inhibitory potential against hOAT1 and hOAT3, suggesting that renal excretion of their substrates could be affected in patients consuming a diet including caffeic acid.
已有研究表明，多种食物会影响药物的吸收和代谢，尽管关于这些食物对药物肾排泄影响的信息还很少。在这项研究中，我们使用非洲爪蟾卵母细胞进行摄取实验，以评估咖啡、水果和蔬菜中含有的绿原酸、咖啡酸和奎尼酸对人有机阴离子转运蛋白 hOAT1 和 hOAT3 的抑制作用；这些转运蛋白介导了阴离子药物从血液向肾小管的摄取。向卵母细胞中注射 hOAT1 和 hOAT3 的 cRNA 可刺激 hOAT1 和 hOAT3 的典型底物（对氨基马尿酸和雌酮硫酸酯）的摄取；在所测试的三种化合物中，咖啡酸对这些转运蛋白的抑制作用最强。咖啡酸对 hOAT1 的 50%抑制浓度（IC50）估计为 16.6µM，对 hOAT3 的 IC50 为 5.4µM。Eadie-Hofstee 作图分析表明，咖啡酸以竞争性方式抑制这两种转运蛋白。除了对对氨基马尿酸和雌酮硫酸酯的转运外，咖啡酸还抑制了抗叶酸剂和抗病毒药物的转运。这些发现表明咖啡酸对 hOAT1 和 hOAT3 具有抑制潜力，提示摄入含有咖啡酸的饮食可能会影响其底物的肾排泄。
