戟叶马鞭草苷大鼠在体肠吸收动力学研究

Study on the Intestinal Absorption Kinetics of Hastatoside in Rats

目的:建立同时测定肠循环液中戟叶马鞭草苷与酚红浓度的高效液相色谱(HPLC)法,探讨戟叶马鞭草苷在大鼠各肠段的吸收动力学特征与不同药物浓度对肠吸收的影响。方法:采用大鼠在体肠灌流吸收实验,以HPLC法对肠循环液中的戟叶马鞭草苷与酚红进行分析。色谱柱为DiamonsilTMC18(250mm×4.6mm,5μm),流动相为乙腈-0.05%磷酸溶液(梯度洗脱),流速为1.0mL·min-1,检测波长为238nm(戟叶马鞭草苷)和430nm(酚红),柱温为30℃。结果:戟叶马鞭草苷浓度在50～200μg·mL-1范围内,其在肠道内的吸收量与浓度成正比例关系。不同药物浓度(50、100、200μg·mL-1)条件下的吸收速率常数(Kα)分别为(69.2±4.3)、(70.9±4.1)、(69.3±3.2)h-1,无显著性差异(P>0.05);在十二指肠、空肠、回肠、结肠的Kα分别为(0.0405±0.0039)、(0.0365±0.0032)、(0.0379±0.0045)、(0.0349±0.0037)h-1,无显著性差异(P>0.05)。结论:戟叶马鞭草苷在大鼠肠道的吸收符合一级动力学过程,吸收机制为被动扩散。戟叶马鞭草苷在整个肠道均有吸收,故可以将其研制成缓、控释制剂。

OBJECTIVE：To develop HPLC method for simultaneous determination of hastatoside and phenolsulfonphthalein in the enterohepatic circulation,and to investigate the absorption kinetics of hastatoside at various intestinal segments of rats and the influence of drug concentration on intestinal absorption kinetics.METHODS：The intestine of rats was cannulated for in situ perfusion.Hastatoside and phenolsulfonphthalein concentration in the circulation was measured by HPLC.The chromatographic procedure was carried out on a DiamonsilTM C18（250 mm×4.6 mm,5 μm） column with mobile phase consisted of acetonitrile-0.05% phosphoric acid solution（gradient elution） at the flow rate of 1.0 mL·min-1.The detection wavelength was set at 238 nm for hastatoside and 430 nm for phenolsulfonphthalein.The temperature of column was 30 ℃.RESULTS：The linear range of hastatoside was 50～200 μg·mL-1,and the uptake of hastatoside was positively correlated with drug concentration.At the concentrations of 50,100 and 200 μg·mL-1 from the whole intestine,the absorption rate constant（Kα） were（69.2±4.3）,（70.9±4.1） and（69.3±3.2）h-1,there was no significant difference（P0.05）.The Kα of hastatoside at duodenum,jejunum,ileum and colon were（0.040 5±0.003 9）,（0.036 5±0.003 2）,（0.037 9±0.004 5） and（0.034 9±0.003 7）h-1,there was no significant difference（P0.05）.CONCLUSION：The absorption of hastatoside in rats＇ intestine is a first-order kinetics process with the passive diffusion absorption mechanism.Hastatoside can be absorbed in whole intestine,so it is suggested that hastatoside could be designed as a sustained-release or controlled-release formulation.