冠心Ⅱ号方不同制备方法对丹参素、阿魏酸在犬体内药代动力学的影响

Study on Pharmacokinetics of Ferulic Acid and Danshensu in Guanxin FormulaⅡ by Different Preparation

目的:研究冠心Ⅱ号方不同制备方法对主要有效成分丹参素、阿魏酸在犬体内药代动力学过程的影响。方法:比格犬分别灌服冠心Ⅱ号全方汤剂(全方混煎制备)和全方有效组分重组复方(全方中各药材有效组分提取物的混合),应用液相色谱-质谱/质谱联用的方法(LC-MS/MS),检测药前及药后不同时间点时血浆中丹参素和阿魏酸的含量。利用药代动力学软件计算药代动力学参数,并进行组间比较。结果:对于丹参素,全方汤剂组达峰浓度(Cmax)和药时曲线下面积(AUC)均显著高于全方有效组分重组复方组(均P<0.05),达峰时间(Tmax)和清除半衰期(t1/2)与全方有效组分重组复方组无显著性差异;而对于阿魏酸,则全方汤剂组的Cmax显著低于全方有效组分重组复方组(P<0.05),Tmax较全方有效组分重组复方组显著延长(均P<0.05),AUC和t1/2与全方有效组分重组复方组比无统计学差异。结论:冠心Ⅱ号全方汤剂的丹参素入血浓度高、生物利用度高,但阿魏酸入血浓度低、达峰时间长,生物利用度低。即冠心Ⅱ号不同制备方法对方中不同有效成分药代动力学过程的影响不同,应结合药效学指标确定最佳制备方法。

Objective: To study the influence of different preparation methods on the pharmacokinetics of main effective components in Guanxin formulaⅡ.Method: Beagle dogs were administrated orally with Guanxin formulaⅡand extracted effective components formula,respecttively.The plasma concentrations of danshensu and ferulic acid were assayed by LC-MS/MS after administration.The pharmacokinetic parameters were estimated by DAS2.0 pharmacokinetics software edited by SunRuiyuan,and then compared within different groups by statistic software SPSS 10.0.Result: As for danshensu,the Cmax and AUC of Guanxin formulaⅡwere significantly higher than the extracted effective components formula,with P<0.05,while Tmax and t1/2 possed no significant difference.But for ferulic acid,the Cmax of the former was significantly lower,while AUC and t1/2 with no statistic difference.Conclusion: The blood concentration and bioavailability of danshensu in Guanxin formularⅡwere higher,but for ferulic acid,they were significantly lower,which indicates that different preparation methods had different impacts on pharmacokinetics,and its parameters should be used to determine the best preparation method.