川芎赤芍配伍比例对阿魏酸在麻醉犬体内药代动力学的影响

Effects of Chuanxiong-Chishao Dispensing Ratio on the Pharmacokinetics of Ferulic Acid in Canine

目的:探索中药配伍比例对中药复方中的药效成分药代动力学特征的影响。方法:采用反相高效液相色谱法紫外检测阿魏酸血清药物浓度,3P87药代动力学软件拟合药代动力学模型,统计学处理采用t检验法。结果:川芎:赤芍1∶2和2∶1芎芍制剂给予麻醉犬灌胃5g·Kg- 1 后阿魏酸的药代动力学过程均符合一室开放模型,川芎∶赤芍1∶2和2∶1组的药动学参数分别为Ka =0 111±0. 0 35 (min- 1 )和0 .0 75±0 . 0 2 0 (min- 1 ) ,Ke=0 . 0 13±0 . 0 0 4 (min- 1 )和0 . 0 16±0 . 0 0 2 (min- 1 ) ,t1 2Ka=6 . 70 1±1 .92 6(min)和9. 735±2 . 377(min) ,t1 2Ke=6. 1 30 6±2 .3 5 31(min)和4. 4 2 5 4±5 .5 18(min) ,tpeak =2 4 . 915±5 . 30 7(min)和2 9 339±4. 10 1(min) ,cmax=5 5 7 .797±172 . 90 3(μg·L- 1 )和15 0 9 .5 18±2 75 . 813(μg·L- 1 ) ;两组间药动学参数Ka与t1 2Ka的差异具有显著统计学意义(P <0 . 0 5 )。结论:川芎赤芍配伍比例对阿魏酸的药动学特征具有显著影响,揭示中药配伍比例的差异有时会导致其中某一种成分的药代动力学特征的变化。

Objective: To explore the effects of dispensing ratio of Chinese herbs on the pharmacokinetics characteristics of effective component.Methods: Ferulic Acid(FA)in serum was determined by RP-HPLC with UV-detector.The concentration-time data were fitted using 3P87 Pharmacokinetic Program,and the pharmacokinetic parameters were compared by t -test.Results: By adminstrating Xiongshao preparation of 5g·kg -1 intragastically, the concentration-time curves of FA in canine groups of Chuanxiong: Chishao=1∶2 and Chuanxiong:Chishao=2∶1 both fitted to open one-compartment model.Parameters of Chuanxiong:Chishao=1∶2 and Chuanxiong:Chishao=2∶1 group were: Ka =0.111±0.035(min -1 ) and 0.075±0.020(min -1 ), Ke =0.013±0.004(min -1 ) and 0.016±0.002(min -1 ), t 1/2Ka = 6.701±1.926(min) and 9.735±2.377(min), t 1/2Ke = 61.306±23.531(min) and 44.254±5.518(min), t peak =24.915±5.307(min) and 29.339±4.101(min), c max =557.797±172.903(μg·L -1 ) and 1509.518±275.813(μg·L -1 )accordingly.The differences of pharmacokinetic parameters Ka and t 1/2Ka between the two groups were statistically significant( P<0.05 ).Conclusion:The difference in dispensing ratio of herbs in Chinese formulae may result in changes of the pharmacokinetic characteristics of the components.