三黄泻心汤及大黄中大黄酸在大鼠体内的药代动力学

Pharmacokinetic Study of Rhein from Sanhuang Xiexin Decoction and Radix et Rhizoma Rhei in Rats

目的:研究三黄泻心汤中大黄酸在大鼠体内的药代动力学规律。比较大鼠灌服三黄泻心汤和单味大黄煎剂后大黄酸的药代动力学特征差异。方法:大鼠灌服三黄泻心汤20生药g.kg-1和单味大黄10生药g.kg-1后,经高氯酸沉淀血浆蛋白、乙醚萃取后,用高效液相色谱法测定大黄酸血药浓度。色谱柱为Shimadzu VP-ODS色谱柱(150 mm×4.6 mm,5μm),流动相为甲醇-0.2%磷酸水溶液(82∶18),流速为1 mL.min-1,检测波长为245 nm,血药浓度-时间数据采用3P97药代动力学软件进行药动学分析。结果:大鼠灌服三黄泻心汤和单味大黄煎剂后,大黄酸血浆浓度-时间曲线均符合二室模型,三黄泻心汤中大黄酸T1/2β(18.26±4.72)h和单味大黄中大黄酸T1/2β(10.69±2.19)h,存在显著性差异(P<0.01);剂量校正后三黄泻心汤和单味大黄大黄酸的Cmax/D分别为(0.82±0.06)μg.mL-1和(0.68±0.04)μg.mL-1,AUC/D分别为(9.05±1.49)(μg.mL-1).h和(6.87±1.60)(μg.mL-1).h,存在显著性差异(P<0.05)。结论:三黄泻心汤中大黄酸的Cmax,AUC,T1/2β值均显著大于单味大黄,说明方剂的药味配伍促进了大黄酸的吸收利用。

Objective： To study the pharmacokinetics of rhein from Sanhuang Xiexin Decoction in rats, and compare the pharmacokinetics of rhein after ig administration of Sanhuang Xiexin Decoction and Radix et Rhiyoma Rhei. Methods： Wistar rats were given（ig） a single dose of Sanhuang Xiexin Decoction 20 g· kg^-1 or Radix et Rhiyoma Rhei 10 g· kg^-1 . The plasma concentration of Rhein was measured by high performance liquid chromatography after extracted with perchlofic acid and ether. An HPLC method was established with （SHIMADZU） VP-ODS column （150 mm × 4.6 mm,5 μm）,the mobile phase was methanol-water-0.2% phosphoric acid （82： 18）, the flow rate was 1.0 mL· min^-1 and a detection wavelength was 245 nm. Pharmacokinetic parameters were determined from the plasma concentration-time data with the software 3P97. Results： The concentration-time curves of rhein fitted well into two-compartment models in rats. The elimination T,2 of rhein in Sanhuang Xiexin Decoction and Radix et Rhiyoma Rhei were （18.26±4.72） h and （10.69± 2.19） h respectively. Significant difference was found between the two groups. There existed significant（ P 〈 0.05） differences in plasma concentration and AUC of rhein between Sanhuang Xiexin Decoction and Radix et Rhiyoma Rhei. The values of normalized AUC by dose of rhein from Sanhuang Xiexin Decoction and Radix et Rhiyoma Rhei were （9.05 ± 1.49） （μg· mL^- 1）· h and （6.87 ± 1.60） （ μg· mL^- 1 ） · h respectively. The values of normalized Cmax by dose of rhein were （0.82 ± 0.06） μg· mL^- 1 and （ 0.68 ± 0.04 ） μg· mL^- 1. Conclusions： The compound compatibility of the decoction promoted the absorption of rhein. It indicated that there is rationality in the compatibility of Sanhuang Xiexin Decoction.