聚乙二醇400对P-糖蛋白底物罗丹明123经肠黏膜的透过性研究

Effect of Polyethylene Glycol 400 on the Permeability of Rhodamine 123,a P-gp Substrate across the Intestinal Mucosa in Rats

目的:研究聚乙二醇400对P-糖蛋白(P-gp)底物罗丹明123(R123)经肠黏膜的透过作用。方法:使用体外扩散池评价R123经空肠、回肠和结肠黏膜的经-时吸收方向和分泌方向的透过量和透过系数(Papp),并测定不同浓度聚乙二醇400对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:R123经肠道黏膜的透过性存在部位差,即以空肠、回肠和结肠的次序透过性依次减少,并且R123经肠道分泌方向的透过性显著地高于其吸收方向的透过性;聚乙二醇400具有增加R123经吸收方向的透过性,但实验浓度的聚乙二醇400对CF的肠道转运没有影响。结论:聚乙二醇400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 effect of polyethylene glycol 400 on the permeability of rhodamine123 （R123） across the intestinal mucosa. METHODS： The absorptive-directed and secretory-directed permeability （Papp） of R123 via rat intestinal membranes from jejunum, ileum to colon was evaluated by an in vitro diffusion chamber system; the effect of polyethylene glycol 400 at different concentrations on the permeability of R123 and that of fluorescein sodium （CF） were determined. And the concentrations of R123 and CF in the receptor were determined by fluorospectrophotometry. RESULTS： There were regional differences for the permeability of R123 across the rat intestinal membranes, i.e. the permeability of R123 decreased in order from jejunum, ileum to colon. Meanwhile, the serosal-to-mucosal permeability （S - M） of R123 was significantly higher than its mucosal-to-serosal （M-S） one. With co-administration of polyethylene glycol 400 at various concentrations, the absorptive- directed transport of R123 was significantly increased. However, at a test concentration, polyethylene glycol 400 showed no effect on the transport of CF across the intestinal membranes. CONCLUSION： Polyethylene glycol 400 could improve the absorption of p-gp mediated drugs though inhibition on P-gp. It is expected to enhance the oral bioavailability of this kind of drugs.