几种表面活性剂对P-gp底物罗丹明123经肠黏膜透过性的影响

 目的观察低浓度表面活性剂聚氧乙烯蓖麻油,Labrasol和聚山梨酯80对肠黏膜P-gp的调控作用。方法使用体外扩散池法评价罗丹明123(R123)经空肠、回肠和结肠黏膜的经时经吸收方向和分泌方向的透过量和透过系数(P_app),并测定不同浓度表面活性剂对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。另一方面,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。低浓度的CEL和Labrasol可显著增强R123经吸收方向的透过性,减少经分泌方向的透过性;而低浓度的聚山梨酯80可显著增强R123经吸收方向的透过性,但对经分泌方向的透过性无显著影响。但实验浓度的表面活性剂对CF的肠道转运没有影响。结论低浓度的聚氧乙烯蓖麻油、Labrasol和聚山梨酯80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。

Effect of Some Surfactants on Permeabilities of Rhodamine 123, a P-gp Substrate Through the Rat Intestinal Membranes in Vitro

OBJECTIVE To investigate the modulation of cremophor EL, labrasol and tween-80 on the permeability characteristics of rhodamine123 (R123) through the different intestinal membranes. METHODS The permeability (P_app) of R123 or fluorescein sodium (CF) via rat intestinal membranes at concentration of 5 mg·L^-1 was evaluated by an in vitro diffusion chamber system after the membranes were isolated from the intestine in rat, with or without the co-administration of the above surfactants at different low concentrations. And the concentration of R123 or CF in the receptor was determined by the fluorospectrophotometry. RESULTS A regional difference was found for the permeability of R123 across the rat intestinal membranes. The permeabilities of R123 was gradually decreased from jejunum, then ileum to colon.On the other hand, the serosal-to-mucosal transport (S-M) of R123 was much higher than its mucosal-to-serosal (M-S) transport. With co-administration of the above respective surfactant at low concentrations, the absorptive directed transport of R123 was significantly increased while its secretory directed transport was decreased. The concentration-dependent effect was found. However, 3 surfactants at tested concentration showed no effect on the transport of CF across the intestinal membranes. CONCLUSION It maybe possible to improve the absorption of P-gp mediated drugs by co-administration of cremophor EL, labrasol and tween-80 at low concentration, therefore to improve the oral bioavailability of these drugs.