目的为探讨穿心莲内酯生物利用度低的原因,考察穿心莲内酯肠道吸收特性,肝肠循环和肠道酶代谢特点。方法采用大鼠在体肠灌流模型。运用HPLC法测定肠灌流液、胆汁以及经肠道酶降解后样品中穿心莲内酯的量。结果穿心莲内酯在不同肠段的吸收率,以十二指肠最高,达40%,而在结肠最低,仅有10%。穿心莲内酯在十二指肠灌流液中的生物降解最显著(1 h降解约50%),在回肠、结肠中则几乎无降解反应。穿心莲内酯有胆汁排泄,其排泄量为灌流药物总量的0.76%。结论穿心莲内酯在大鼠肠道的吸收较差,而在十二指肠中吸收表现较好是由于存在较强的肠道酶代谢作用。同时,穿心莲内酯存在明显的肝肠循环。穿心莲内酯生物利用度低的原因与肠吸收差、肠道酶代谢作用强和肝肠循环有关。

Objective To investigate the causes of poor bioavailability of andrographolide,the absorption characteristics,hepatic-enteric recycling,and metabolism of andrographolide in rat intestines were observed.Methods A single-pass "four-site" rat intestinal perfusion model in situ was employed.The concentration of andrographolide in perfusates,bile,and in vitro incubation samples for metabolites of andrographolide by the intestinal enzymes,respectively,was determined by HPLC.Results In the perfusion model,maximal absorption of andrographolide occurred in the duodenum with a 40% absorption rate,whereas only 10% of andrographolide was absorbed in the colon.Moreover,andrographolide was rapidly hydrolyzed(about 50% in 1 h) in the duodenum perfusates but was not hydrolyzed at all in the colon and ileum perfusates.On the other hand,andrographolide was excreted by bile with a total of 3.04% prefused amount of andrographolide.Conclusion The poor absorption,rapidly hydrolysis,and hepatic-enteric recycling in the intestine all contribute to the poor bioavailability of andrographolide.

国家“十一五”支撑计划项目(2006BAI11B08-04);广东省高等学校自然科学研究重点项目(06Z008);广州市科学技术局应用基础项目(2007JI-C0021)