大鼠在体肠灌流模型中补骨脂素的吸收研究

目的:研究补骨脂素在大鼠小肠的吸收特性及其机制,探讨其在临床上血药浓度差异较大的原因。方法:采用改良大鼠在体单向肠灌流模型,通过颈静脉插管补充血液、肠系膜静脉插管采集血样,同时收集灌流流出液,以反相高效液相色谱法测定补骨脂素含量,计算其通透率。结果:补骨脂素在大鼠小肠内通透率较高,吸收较好。不同浓度的补骨脂素灌流时均以约30%的比例吸收入血,且通透率Plumen,Pblood在所测浓度范围内基本保持不变。结论:补骨脂素在大鼠小肠的转运机制为被动转运,不受P-糖蛋白的影响,临床上血药浓度个体差异大可能与肝脏的首过效应有关,而非小肠吸收代谢所致。

In vivo absorption of psoralen using improved rat intestinal perfusion model

Aim:To investigate the absorption characteristics and involved mechanism of psoralen in the rat intestine in order to clarify the reason of great variability of plasma concentration in clinical treatment.Methods:The rat single-pass intestinal perfusion model with jugular vein cannulated was used.Samples were obtained continuously from the outlet perfusate and the mesenteric vein at 5 min intervals in 60 min.The level of psoralen was determined by RP-HPLC and the permeability coefficients were calculated.Results:Psoralen exhibited a high intestinal permeability indicative of compound that was well absorbed.About thirty percent of psoralen was absorbed into mesenteric vein despite the inlet perfusate concentrations.No significant differences in intestinal psoralen inlet coefficients were observed at different psoralen inlet concentrations(P>0.05).Conclusion:Psoralen had a high intestinal permeability across the rat intestine via the mechanism of passive diffusion,and P-glycoprotein mightily was not involved in the transport process.The occurrence of variations in psoralen plasma levels in clinical treatment was probably due to hepatic first-pass effect rather than intestinal absorption factors.