大黄黄连泻心汤不同配伍下黄芩苷和汉黄芩苷在大鼠体内的药动学比较研究

Effects of Different Dahuang Huanglian Xiexin Decoction Formulations on the Pharmacokinetics of Baicalin and Wogonoside in Rats

目的:比较大黄黄连泻心汤不同配伍情况下黄芩有效成分黄芩苷和汉黄芩苷在大鼠血浆中的药动学差异。方法:大鼠灌服以黄芩、大黄黄芩、黄连黄芩、大黄黄连黄芩的不同配伍浸渍提取液,于不同时间点采血,经处理后测定血浆中黄芩苷和汉黄芩苷的含量,计算在不同配伍情况下的药动学参数并进行比较分析。结果:在大黄黄连泻心汤的不同配伍中,黄芩配伍大黄后,黄芩主要成分原有的药时曲线双峰现象消失,Cmax及AUC均明显下降,消除过程加快;在配伍黄连后,黄芩主要成分的体内过程与单味黄芩相似,只是第2吸收峰有增高的趋势;大黄、黄连和黄芩3味药配伍时,黄芩主要成分的达峰浓度Cmax及AUC均明显下降,消除减慢。结论:在大黄黄连泻心汤的不同配伍中,大黄、黄连的加入使得黄芩中的主要成分黄芩苷和汉黄芩苷的药动学特征发生显著改变,大黄可减少黄芩苷、汉黄芩苷的吸收,加快其消除,而黄连则削弱了大黄的作用。

This study was aimed to examine effects of Dahuang （DH） and Huanglian （HL） on the pharmacokinetics of baicalin and wogonoside, which are major bioactive chemicals of Huangqin （HQ）, in rats after administering HQ alone and HQ in combination with DH and/or HL. Rats were administered a single oral dosage of HQ or HQ in combination with DH and/or HL. Blood samples were taken at different time points post-dosing and analyzed for baicalin and wogonoside using HPLC-UV. The plasma concentration-time curves were compared and analyzed. The results showed that the absorption of baicalin and wogonoside were rapid and can be described by two characteristic absorption peaks in HQ group. After the administration of DH-HQ to rat, the secondary absorption peaks of both baicalin and wogono- side plasma concentration-time profiles disappeared completely with the decrease of C~ and AUC, as well as a short- en action time. The total exposure level of flavones in plasma was not changed after combining with HL, while C,~ of wogonoside increased remarkably. In DH-HL-HQ combination, C,~1 of baicalin and wogonoside as well as CL/F and AUC of baicalin were reduced significantly. It was concluded that the absorption of baicalin and wogonoside are de- creased by DH and increased by HL. HL may weaken the effect of DH that inhibits the absorption and increases the clearance as well as enlarges the distribution of baicalin and wogonoside.