冠心苏合丸中土木香替代青木香的比较药动学研究

Comparative pharmacokinetics of active component in Guanxin Suhe Pills containing Radix Inulae in place of Radix Aristolochiae

目的比较冠心苏合丸系列组方(含青木香的冠心苏合丸、含土木香的冠心苏合丸及不含木香的冠心苏合丸)灌胃比格犬后,其有效成分肉桂酸药动学过程的差异。方法建立高效液相色谱法测定健康比格犬血浆中肉桂酸的方法;采集比格犬灌服冠心苏合丸系列组方后0～8 h的血浆,测定血药浓度;用DAS2.1软件模拟房室模型并计算药动学参数。结果含肉桂酸的血浆样品在0.031 25～32 mg/L与峰面积的线性关系良好(r=0.999 96);最低检测限为31.25μg/L;提取回收率在90%以上;日内精密度与日间精密度均小于5%。含青木香、含土木香以及不含木香的3种冠心苏合丸中有效成分肉桂酸在犬体内均符合一级吸收双室模型;含土木香冠心苏合丸以及不含木香冠心苏合丸组的肉桂酸峰浓度和药时曲线下面积有大于含青木香冠心苏合丸组的趋势,但三者之间无显著性差异。结论比格犬灌服冠心苏合丸系列组方后,血浆中有效成分肉桂酸的药动学过程大体一致,原方中的青木香被土木香替换或者去掉青木香,对该药主要有效成分肉桂酸的药动学过程无明显影响。

Objective To study the pharmacokinetics of the active component in series of Guanxin Suhe Pills including the prescription containing Radix Aristolochiae （QG）, the prescription containing Radix Inulae （TG）, and the prescription without any of them （BG） in Beagle dogs and to compare the pharmacokinetics among the series of prescription. Methods HPLC Method was developed to determine acid in plasma of Beagle dogs. Blood plasma was collected after series of Guanxin Suhe Pills were ig administrated to Beagle dogs 0-8 h later. The concentration of cinnamic acid in the plasma was determined and DAS 2.1 software was used in calculation of compartment model and pharmacokinetic parameters. Results The standard curve was linear from 0. 031 25 to 32 mg/L in plasma of Beagle dogs, the lowest detectable limit was 31.25 μg/L, the recovery rate of the method was over 90 % with satisfactory relative standard deviations （RSDs） of intra-day and inter-day both lower than 5 %. The metabolism of cinnamic acid in plasma of Beagle dogs after medication of series in QG, TG, and BG all fitted in a first order absorption of two-compartment model. The peak concentration and the area under curve in TG and BG groups had the higher tendency than those in the QG group, but there was no significant difference among the three groups. Conclusion The series of Guanxin Suhe Pills all have a similar pharmacokinetic process. Taking away the Radix Aristolochiae from the previous prescription that including the Radix Aristolochiae or taking the place of the Radix Aristolochiae with Radix Inulae does not influence the pharmacokinetic process of the main active component.