冬凌草甲素大鼠在体肠吸收动力学研究

Studies on Absorption Kinetics of Oridonin in Rat Intestines

目的研究冬凌草甲素在大鼠各肠段的吸收动力学特征,建立同时测定肠循环液中冬凌草甲素及酚红浓度的HPLC/DAD法,探讨冬凌草甲素在大鼠各肠段的吸收动力学特征及不同药物浓度对其的影响。方法采用大鼠在体肠吸收实验方法,用HPLC对循环液中的冬凌草甲素进行分析。结果在5.0-15.0μg·mL^-1内冬凌草甲素的吸收速率与质量浓度呈线性关系,Ka值基本保持不变;各肠段的吸收速率无显著性差异,十二指肠、空肠、回肠、结肠的Ka值分别为（0.047 5±0.0062）,（0.046 8±0.005 1）,（0.034 6±0.003 7）,（0.043 5±0.002 3）h^-1。结论冬凌草甲素在肠道的吸收呈现一级动力学过程,且吸收机制为被动扩散;冬凌草甲素在整个肠道均有吸收,可以将冬凌草甲素研制成缓释制剂。

OBJECTIVE To investigate the absorption kinetics of oridonin at different intestine segments in rats,and develop a high-performance liquid chromatography coupled with diode array detection（HPLC/DAD） method to determine the contents of oridonin and phenolsulfonphthalein.METHODS The intestine in rats was cannulated for in situ recirculation.HPLC was used to determine simultaneously the concentrations of phenolsulfonphthalein and oridonin,respectively.RESULTS When the concentration was increased from 5.0 to 15.0 μg·mL^-1,the uptake of oridonin was increased linearly.The concentration had no effect on the permeability coefficient.The permeability coefficients of oridonin at duodenum,jejunum,ileum and colon were（0.047 5±0.006 2）,（0.046 8±0.005 1）,（0.034 6±0.003 7） and（0.043 5±0.002 3）h^-1,respectively.CONCLUSION The absorption rate of oridonin in rat intestine is a first-order process with the passive diffusion mechanism.Oridonin can be absorbed in whole intestinal segments,so oridonin sustained-released formulations can be prepared.