维拉帕米对P-糖蛋白底物罗丹明123经空肠黏膜透过性的影响

Effect of verapamil on the permeability of the P-glycoprotein substrate rhodamine 123 across the jejunal membranes

目的:研究维拉帕米对肠黏膜P-糖蛋白(P-gp)的调控作用。方法:使用体外扩散池测定不同浓度维拉帕米对P-gp底物罗丹明123(R123)和荧光素钠(CF)经肠黏膜透过性的影响。R123和CF在接受室中的浓度用荧光分光光度法测定。结果:维拉帕米具有增加R123经吸收方向的透过性,并且减少分泌方向的渗透性。但实验浓度的维拉帕米对CF的肠道转运没有影响。结论:维拉帕米可通过对P-gp功能的抑制而用于改善受P-gp介导药物的吸收,有望提高此类药物的口服生物利用度。

Objective To investigate the role of verapamil in the regulation of P-glycoprotein （P-gp） across the jejunal membranes. Methods The effect of veraparmil at different concentrations on the permeability of rhodamine （R123） or fluorescein sodium （CF） across the jejunal membranes was evaluated using an in vitro diffusion chamber system. The concentration of R123 or CF in the receptor chamber was determined by fluorospectrophotometry. Results Verapamil increased the serosal-to-mucosal （S-M） transport of R123 but decreased its opposite transport; however, it had no impact on the transport of CF across the intestinal membranes. Conclusion Verapamil may improve the P-gp mediated-drug transport by inhibiting P-gp function, therefore, enhancing the oral bioavailability of the medications mediated by P-gp.