熊果酸灌胃给药大鼠体内药代动力学研究

Pharmacokinetics in Vivo of Ursolic Acid by Intragastric Administration in Rats

目的研究熊果酸在大鼠体内的药代动力学特征。方法 10只SD大鼠给予熊果酸20 mg/kg单次灌胃,采用高效液相色谱（HPLC）法测定熊果酸的血药浓度,检测波长为221 nm,流动相为乙腈-0.1%磷酸水溶液（78.5∶21.5）。采用DAS 2.1.1药动学软件计算熊果酸的主要药代动力学参数。结果熊果酸进样质量浓度线性范围为0.05~50.00μg/m L（r=0.999 5）,方法回收率为97.63%~102.42%,日内和日间精密度的RSD均小于12%（n=6）。熊果酸的大鼠体内过程符合一室模型,峰浓度（Cmax）为（35.64±8.63）μg/m L,消除半衰期（t1/2）为（4.421±1.835）h,0~18 h药时曲线下面积（AUC0-18）为（15.52±3.387）μg·h/m L,0~∞药时曲线下面积（AUC0-∞）为（28.540±6.172）μg·h/m L。结论所建立的HPLC法准确、灵敏、快速,适用于熊果酸的血药浓度测定;熊果酸的药代动力学参数为其制剂研究奠定了良好的基础。

Objective To study the pharmacokinetic characteristics in vivo of ursolic acid in rats. Methods 10 SD rats were given ur-solic acid 20 mg/kg by once gavage. Plasma ursolic acid concentration was determined by HPLC at the wavelength of 221 nm. The mixture of acetonitrile-0. 1% phosphoric acid （ 78. 5 ：21. 5 ） was used as the mobile phase. And the main pharmacokinetic parameters of ursolic acid were calculated with the DAS 2. 1. 1 software. Results The mass concentration linear range of ursolic acid sample size was 0. 05-50. 00 μg/mL （ r=0. 999 5 ） . The method recovery rate was 97. 63% -102. 42%. Both the within-day and between-day RSD were less than 12%（ n=6 ） . The rat in vivo process of ursolic acid was fitted to one-compartment open pharmacokinetic model. The main pharmacokinetic parameters were as follows： Cmax was （35. 64 ±8. 63）μg/mL,t1/2 was （4. 421 ±1. 835）h,AUC0-18 was （15. 52 ± 3. 387 ）μg · h/mL,AUC0 -∞ was （ 28. 540 ± 6. 172 ）μg · h/mL. Conclusion The established HPLC method is accurate,sensitive and rapid,and can be used for the blood concentration determination of ursolic acid; the pharmacokinetic parameters of ursolic acid pro-vides a good foundation for the study on the ursolic acid preparation.