摘要
目的考察α-常春藤皂苷的肠道吸收特性,探讨α-常春藤皂苷生物利用度低的原因。方法采用大鼠在体肠单向灌流模型、运用HPLC法测定药物的质量浓度,分别研究吸收部位、药物质量浓度、pH值、肠道菌群以及P-糖蛋白(P-gp)抑制剂对α-常春藤皂苷吸收的影响。结果α-常春藤皂苷在不同肠段的吸收速率常数(Ka)顺序为回肠>结肠>空肠>十二指肠;且以质量浓度为75、150、300μg/mL的供试液进行实验,Ka和Peff没有显著性差异;药物的吸收随pH值升高而增加;扰乱大鼠肠道菌群会干扰α-常春藤皂苷的吸收;含P-gp抑制剂组和不含P-gp抑制剂组相比,α-常春藤皂苷的Ka和Peff值均无显著性差异。结论α-常春藤皂苷在全肠道均有吸收,但在肠道下部吸收较好;在实验质量浓度范围内,药物的吸收无浓度饱和现象,吸收机制为被动扩散;药物在碱性环境下吸收较好;肠道菌群对α-常春藤皂苷吸收有显著影响;α-常春藤皂苷不是P-gp底物。
Objective To investigate the intestinal absorption characteristics of α-hederin and to explore the causes of poor bioavailability. Methods In vivo single-pass perfusion model was used and the concentration of α-hederin was determined by HPLC. The effects of intestinal segment, drug concentration, pH value, gut microflora, and P-gp inhibitor on the intestinal absorption of the drug were investigated. Results The absorption rate constant （Ka） of α-hederin decreased following the sequence of ileum 〉 colon 〉 jejunum 〉 duodenum. Absorption parameters of α-hederin had no significant difference at different concentration of 75, 150, and 300 μg/mL and those increased with the increase of pH value. The intestinal flora which were disrupted may affect the absorption of α-hederin. There was no significant difference in Ka and Pelf values between P-gp inhibitor and no P-gp inhibitor groups. Conclusion α-Hederin can be absorbed in whole intestine, but better in lower intestine. The saturate phenomena was not observed under the test range of drug concentration, and the absorption mechanism may be the passive diffusion transport. The absorption can be better under basic condition. The absorption is significantly affected by the intestinal flora and α-hederin is not the substrate of P-gp.
出处
《中草药》
CAS
CSCD
北大核心
2014年第6期807-812,共6页
Chinese Traditional and Herbal Drugs
基金
国家"重大新药创制"科技重大专项(2012ZX09103201-008)
江西省科技支撑计划项目(20111BBG70005-2)
江西省自然科学基金(20114BAB215046)
江西中医药大学博士启动基金(Y055)
江西省卫生厅项目(2012A028)
南昌市科技支撑计划(洪财企[2012]80号社发支撑-3)
关键词
α-常春藤皂苷
单向灌流法
在体肠吸收
肠道菌群
被动扩散
α-hederin
single-pass perfusion method
in vivo intestinal absorption
gut microfiora
passive diffusion
