Abstract：
BACKGROUND: Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway.
METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry.
RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability.
CONCLUSIONS: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.
METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry.
RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability.
CONCLUSIONS: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.
摘要：
背景：一些葡萄糖苷药物可以通过肠道葡萄糖转运蛋白（IGTs）运输，和碳水化合物赋形剂在药物制剂中的存在可能影响它们的吸收。这项研究,使用天麻素作为探针药物，旨在探索果糖的影响，乳糖,和阿拉伯树胶对肠道药物吸收介导的葡萄糖转运途径。
方法：果糖的影响，乳糖,通过药代动力学实验和单次肠道灌注评估阿拉伯树胶对天麻素的吸收。通过RT-qPCR和蛋白质印迹定量钠依赖性葡萄糖转运蛋白1（SGLT1）和钠非依赖性葡萄糖转运蛋白2（GLUT2）的表达。通过H&E染色评估大鼠肠通透性的改变，RT-qPCR,和免疫组织化学。
结果：果糖使天麻素的曲线下面积（AUC）和峰浓度（Cmax）分别降低了42.7％和63.71％，分别为(P<0.05)，并降低十二指肠和空肠的有效渗透系数（Peff）58.1%和49.2%，分别为(P<0.05)。SGLT1和GLUT2表达和肠通透性保持不变。乳糖使天麻素的AUC和Cmax分别提高了31.5%和65.8%,分别为(P<0.05)，并使十二指肠和空肠中的Peff分别增加了33.7％和26.1％，分别为(P<0.05)。SGLT1和GLUT2水平没有显著差异，肠道通透性增加。阿拉伯胶对药代动力学参数没有显着影响，SGLT1或GLUT2表达，或肠道通透性。
结论：果糖，乳糖,和阿拉伯树胶通过葡萄糖转运途径不同程度地影响肠道药物的吸收。果糖竞争性抑制药物吸收，而乳糖可以通过增加肠道通透性来增强吸收。阿拉伯树胶没有显著影响。
方法：果糖的影响，乳糖,通过药代动力学实验和单次肠道灌注评估阿拉伯树胶对天麻素的吸收。通过RT-qPCR和蛋白质印迹定量钠依赖性葡萄糖转运蛋白1（SGLT1）和钠非依赖性葡萄糖转运蛋白2（GLUT2）的表达。通过H&E染色评估大鼠肠通透性的改变，RT-qPCR,和免疫组织化学。
结果：果糖使天麻素的曲线下面积（AUC）和峰浓度（Cmax）分别降低了42.7％和63.71％，分别为(P<0.05)，并降低十二指肠和空肠的有效渗透系数（Peff）58.1%和49.2%，分别为(P<0.05)。SGLT1和GLUT2表达和肠通透性保持不变。乳糖使天麻素的AUC和Cmax分别提高了31.5%和65.8%,分别为(P<0.05)，并使十二指肠和空肠中的Peff分别增加了33.7％和26.1％，分别为(P<0.05)。SGLT1和GLUT2水平没有显著差异，肠道通透性增加。阿拉伯胶对药代动力学参数没有显着影响，SGLT1或GLUT2表达，或肠道通透性。
结论：果糖，乳糖,和阿拉伯树胶通过葡萄糖转运途径不同程度地影响肠道药物的吸收。果糖竞争性抑制药物吸收，而乳糖可以通过增加肠道通透性来增强吸收。阿拉伯树胶没有显著影响。
