[关键词]
[摘要]
目的 考察白头翁皂苷D在大鼠肠道的吸收特性。方法 采用大鼠在体单向肠灌流模型考察白头翁皂苷D在大鼠肠道的吸收情况,HPLC法测定肠灌流液中的白头翁皂苷D,以白头翁皂苷D的吸收速率常数(Ka)和表观渗透系数(Papp)为指标,考察吸收部位、药物浓度、pH值和P-糖蛋白(P-gp)抑制剂对白头翁皂苷D吸收的影响。结果 白头翁皂苷D灌流液在各肠段的Ka和Papp值为结肠>回肠>空肠>十二指肠,且各肠段之间存在显著差异(P<0.05);随着pH值不断增加,Ka和Papp值也随之增加,且Ka和Papp均存在显著差异(P<0.05);不同质量浓度(0.30、0.15、0.08 mg/mL)的灌流液在结肠的吸收无显著差异;灌流液中含P-gp抑制剂与不含P-gp抑制剂的白头翁皂苷D的肠吸收存在显著差异(P<0.05)。结论 白头翁皂苷D在大鼠各肠段均能较好地被吸收,吸收窗主要在结肠;一定范围内的药物质量浓度对白头翁皂苷D的Ka和Papp无明显影响,初步确定其吸收机制为被动扩散;白头翁皂苷D是P-gp的底物,且存在转运蛋白饱和现象。
[Key word]
[Abstract]
Objective To investigate the intestinal absorption characteristics of Pulsatilla saponin D in rats. Methods In situ single-pass intestinal perfusion model was used to inspect the absorption of Pulsatilla saponin D in the intestinal tract of rats. HPLC was used to determine the concentration of Pulsatilla saponin D in intestinal perfusion fluid samples. Absorption rate constant (Ka) and apparent permeability coefficient (Papp) were used as indexes to investigate the effects of absorption sites, drug concentration, different pH values, and P-glycoprotein (P-gp) inhibitor on Pulsatilla saponin D absorption. Results There was the significant difference (P < 0.05) of intestinal perfusion fluid samples in each intestinal segment and the order of the Ka and Papp values of Pulsatilla saponin D in each intestinal segment was colon > ileum > jejunum > duodenum. With the pH value increasing, the Ka and Papp values also increased and both of them had significant differences (P < 0.05). The colon absorption of perfusion fluid at different concentration (0.30, 0.15, and 0.08 mg/mL) had no significant difference (P > 0.05); There was significant difference (P < 0.05) in Ka and Papp values with and without P-gp inhibitor. Conclusion Pulsatilla saponin D could be well absorbed in whole intestinal segments of rats, and the best intestinal absorption site is colon; The drug concentration in a certain range has no effect on Ka and Papp values, which preliminarily comfirms that the obsorption mechanism of Pulsatilla saponin D could be passive diffusion; Pulsatilla saponin D may be a substrate of P-gp and possess the saturation phenomenon of transporters.
[中图分类号]
[基金项目]
国家“重大新药创制”科技重大专项(2011ZX11102-001-19);江西省自然科学基金资助项目(20114BAB215045);江西省优势科技创新团队计划项目(2010DQB01700);江西省教育厅产学研合作项目(GJJ11006)