Diclofenac is an extensively used nonsteroidal anti-inflammatory drug, but gastrointestinal liabilities and cardiovascular complications take the shine away from such a widely prescribed drug. On the other hand, rutin, a dietary bioflavonoid, has quite a few pharmacological attributes to improve the efficacy and reduce the dose-related toxicities of diclofenac through the intended food-drug/herb-drug interaction.

The aim of the present research work was to investigate the role of rutin on pharmacokinetic modulation and the consequent efficacy of diclofenac.

At first, pharmacodynamics and pharmacokinetics of diclofenac as alone and in the presence of rutin were investigated orally in a rat model. Then, mechanistic studies were performed to explain the effect of rutin on improvement in oral exposure as well as the efficacy of diclofenac using a battery of in-vitro/in-situ/in-vivo studies.

Results displayed that rutin enhanced efficacy as well as oral bioavailability of diclofenac in rats. A marked increase in permeability of diclofenac by rutin was displayed that is linked to inhibition of Breast Cancer Resistance Protein (BCRP) transporters. There was no significant effect of rutin on the modulation of intestinal transit, CYP2C9 inhibition in human liver microsomes, and CYP2C9/CYP2C11 expression in rat liver tissues to boost the oral exposure of diclofenac.

Rutin is found to be an inhibitor for BCRP transporters and can act as an oral bioavailability enhancer for a drug like diclofenac.

双氯芬酸是一种广泛使用的非甾体类抗炎药，但胃肠道疾病和心血管并发症使这种广泛使用的药物失去了光泽。另一方面，膳食生物类黄酮芦丁具有相当多的药理特性，可通过预期的食品-药物/草药-药物相互作用来改善双氯芬酸的功效并降低剂量相关的毒性。

本研究工作的目的是研究芦丁在药代动力学调节中的作用以及双氯芬酸的功效。

首先，在大鼠模型中口服研究了双氯芬酸单独和在存在芦丁的情况下的药效学和药代动力学。然后，通过一系列的体内/原位/体内研究进行了机理研究，以解释芦丁对改善口腔暴露的作用以及双氯芬酸的功效。

结果显示芦丁增强了双氯芬酸在大鼠中的功效以及口服生物利用度。芦丁显示双氯芬酸的通透性显着增加，这与抑制乳腺癌抵抗蛋白（BCRP）转运蛋白有关。芦丁对大鼠肝组织中肠运输的调节，CYP2C9的抑制以及大鼠肝组织中CYP2C9 / CYP2C11的表达对双氯芬酸的口服暴露没有显着影响。

发现芦丁是BCRP转运蛋白的抑制剂，可作为双氯芬酸等药物的口服生物利用度增强剂。