氢溴酸高乌甲素大鼠在体胃肠的吸收动力学研究

Absorption kinetics of lappaconite hydrobromide in rat stomachs and small intestines

目的:考察氢溴酸高乌甲素(LH)在大鼠胃肠道的吸收动力学特征及促进剂对其的吸收促进效果。方法:采用大鼠在体胃肠吸收实验模型,用HPLC法测定循环液中药物的浓度。结果:LH在胃、十二指肠、空肠、回肠、结肠的吸收百分率分别为9.67%,19.61%,11.83%,12.95%,9.51%;不同质量浓度的LH(10～40 mg.L-1)与小肠吸收量呈线性关系,吸收速率常数Ka几乎不变。P-糖蛋白抑制剂维拉帕米可增加药物从小肠的吸收。促进剂对药物在小肠内的吸收促进效果均比较明显,癸酸钠吸收促进效果最好。组织病理学观察结果显示,癸酸钠对小肠黏膜造成的损伤最小。结论:药物在整个胃肠道中的吸收均比较有限,在小肠中的吸收呈一级动力学过程,吸收机制有可能为被动扩散;吸收促进剂癸酸钠吸收促进效果最好,且毒性最小,有望作为药用辅料用于口服制剂中提高LH的生物利用度。

Objective：To study absorption kinetics of lappaconite hydrobromide in rat stomachs and intestines.Methods： Rats were cannulated for in situ recirculation.HPLC method was used to determine the concentration of lappaconite hydrobromide.Results： The absorption percentage in rat stomachs after administration was 9.67%.The absorption percentages at duodenum,jejunum,ileum and colon were 19.61%,11.83%,12.95% and 9.51%,respectively.When the concentration was raised from 10 mg·L^-1 to 40 mg·L^-1,the uptake of lappaconite hydrobromide was linearly increased,whereas the absorption rate constant kept at the same level.The inhibitors of P-glycoprotein had obvious effects on the absorption in small intestines.Sodium caprate was the best enhancer that did not cause significant changes in the morphology of the intestinal membrane after intestinal administration as compared with other absorption enhancers.Conclusion： The absorption of LH in the whole gastrointestinal tract is relatively limited.It is a first-order process with passive diffusion mechanism.We suppose that sodium caprate seems to be a good candidate of excipient for enhancing the oral bioavailability of LH.