School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
Chin J Nat Med. 2014 Feb;12(2):131-8. doi: 10.1016/S1875-5364(14)60021-2.
A significant number of organic carboxylic acids have been shown to influence the absorption and distribution of drugs mediated by organic anion transporters (OATs). In this study, uptake experiments were performed to assess the inhibitory effects of cinnamic acid, ferulic acid, oleanolic acid, deoxycholic acid, and cynarin on hOAT1, hOAT3, hOATP1B1, and hOATP2B1. After a drug-drug interaction (DDI) investigation, cinnamic acid, ferulic acid, deoxycholic acid, and cynarin were found and validated to inhibit hOAT1 in a competitive manner, and deoxycholic acid was found to be an inhibitor of all four transporters. The apparent 50% inhibitory concentrations of cinnamic acid, ferulic acid, deoxycholic acid, and cynarin were estimated to be 133.87, 3.69, 90.03 and 6.03 μmol·L(-1) for hOAT1, respectively. The apparent 50% inhibitory concentrations of deoxycholic acid were estimated to be 9.57 μmol·L(-1) for hOAT3, 70.54 μmol·L(-1) for hOATP1B1, and 168.27 μmol·L(-1) for hOATP2B1. Because cinnamic acid, ferulic acid, and cynarin are ingredients of food or food additives, the present study suggests there are new food-drug interactions to be disclosed. In addition, deoxycholic acid may be used as a probe for studying the correlation of OATs and OATPs.
大量的有机羧酸已被证明会影响有机阴离子转运体（OATs）介导的药物的吸收和分布。在这项研究中，进行了摄取实验以评估肉桂酸、阿魏酸、齐墩果酸、去氧胆酸和水飞蓟宾对 hOAT1、hOAT3、hOATP1B1 和 hOATP2B1 的抑制作用。在进行药物相互作用（DDI）研究后，发现肉桂酸、阿魏酸、去氧胆酸和水飞蓟宾以竞争性方式抑制 hOAT1，并验证了去氧胆酸是四种转运体的抑制剂。肉桂酸、阿魏酸、去氧胆酸和水飞蓟宾抑制 hOAT1 的表观 50%抑制浓度分别估计为 133.87、3.69、90.03 和 6.03 μmol·L(-1)。去氧胆酸对 hOAT3 的表观 50%抑制浓度估计为 9.57 μmol·L(-1)，对 hOATP1B1 的表观 50%抑制浓度估计为 70.54 μmol·L(-1)，对 hOATP2B1 的表观 50%抑制浓度估计为 168.27 μmol·L(-1)。由于肉桂酸、阿魏酸和水飞蓟宾是食物或食品添加剂的成分，本研究表明存在新的食物-药物相互作用需要披露。此外，去氧胆酸可用作研究 OATs 和 OATPs 相关性的探针。
