门静脉吸收动力学模型与大黄蒽醌在正常大鼠体内吸收动力学研究

Study on portal vein absorption kinetics model and rhubarb anthraquinones absorption kinetics in normal rats

目的:探索门静脉吸收动力学模型应用的可行性,并考察大黄游离蒽醌在大鼠门静脉的吸收动力学特征。方法:正常大鼠十二指肠给予大黄游离蒽醌,同时采集门静脉和颈总静脉血液,采用反相离子对高效液相色谱法测定血浆中五种游离蒽醌的浓度。首次提出了门静脉吸收动力学模型,以门静脉浓度与颈总静脉浓度差值表示药物吸收浓度,并在此基础上采用统计矩法计算吸收动力学参数。结果:门静脉血浆中大黄素甲醚仅在个别动物少数时间点可以检测到,大黄素与大黄酚多数浓度都低于最低定量限;颈总静脉血浆中仅大黄酸浓度高于最低定量限。因此,本文仅对芦荟大黄素和大黄酸的血药浓度进行了吸收动力学参数的计算。结论:应用门静脉吸收动力学模型研究药物的吸收动力特征方法可行。芦荟大黄素和大黄酸在正常大鼠体内的吸收具有性别差异;二者属于慢吸收化合物;研究提示芦荟大黄素在肝脏内具有代谢过程。

Objective:To investigate the feasibility of portal vein absorption kinetics model and study the portal vein absorption kinetics of free Rhubarb anthraquinones in rat after duodenal injection.Method:Reversed phase ion-pair HPLC was used to determine the concentration of free rhubarb anthraquinones in rat portal vein and carotid vein plasma.All absorption kinetic parameters were calculated by MATLAB2007B with the statistic moment theory.Result:Physcion were detected only in some individual rat at individual time points,and most of the concentration of emodin and chrysophanol were lower than the limit of quantitation.Therefore,the absorption kinetic parameters of aloe-emodin and rhein were calculated in this paper.Conclusion:Aloe-emodin and rhein absorption in normal rats have gender differences.Aloe-emodin and Phein are absorbed slowly in portal vein and the research suggests that aloe-emodin may be metabolized in liver.