地格达-4味汤中獐牙菜苦苷在急性肝损伤模型大鼠体内药代动力学研究

目的:建立急性肝损伤模型大鼠血清中獐牙菜苦苷的HPLC血药浓度测定方法,并对其药代动力学进行研究.方法:SD大鼠腹腔注射D-半乳糖胺(D-GIaN) (400 mg·kg-1),制备急性肝损伤模型,按高、中、低(0.39,0.77,1.54 g·kg-1)剂量灌胃给予地格达-4味汤,收集不同时间点含药血清,HPLC测定血药浓度,采用Winnonlin 5.1药动学软件拟合房室模型,计算其药动学参数.结果:獐牙菜苦苷在0.000 6 ～0.019 2 mg ·L-1(r =0.998 9)线性关系良好,平均回收率均在80％以上,方法学考察其他项均符合实验要求.地格达-4味汤高、中、低剂量组吸收半衰期基本一致,药时曲线下面积(AUC)与给药剂量之间呈现良好的线性关系,属于线性动力学过程.结论:獐牙菜苦苷在急性肝损伤模型大鼠体内的药时曲线符合二室模型特征；所建立的方法准确,灵敏度高,专属性好,可作为獐牙菜苦苷体内血清药物浓度分析方法.

Pharmacokinetics Study of Swertiamain of Mongolian Medicine DIGEDA-4 Decoction in Acute Liver Lesion Rat

Objective:To establish a high performance liquid chromatography(HPLC) method for determining the serum concentration of swertiamain in acute liver damage rat and to investigate pharmacokinetics of swertiamain.Method:The model of acute liver damage rat was established by D-galactosamine(D-GIaN) 400 mg·kg-1 intraperitoneal injection.After the rats were administered by DIGEDA-4 decoction,HPLC was used to determine the serum concentration of swertiamain at different times;Winnonlin 5:1 procedure was used to calculate concentration-time data and pharmacokinetic parameters.Result:The linearity were ranged from 0.15-4.8 μg ·L-1(r=0.998 9) and the average recovery was higher than 80%.Methodology investigation was all complied with the requirements.After oral administration of DIGEDA-4 decoction,the T1/2 was similar,the relationship between dose and AUC showed good linearity.Conclusion:The swertiamain was fitted to be a two-compartment model in acute liver damage rat.The method described in this report was accurate and has high sensitivity and selectivity which can be used to analyze quantitatively the serum concentration of swertiamain of the DIGEDA-4 decoction.