川白芷提取物异欧前胡素大鼠体内药动学研究

【摘要】  目的 探讨经灌胃给药后川白芷提取物异欧前胡素大鼠体内的药物动力学特征。方法 采用高效液相色谱法,测定灌胃给药后大鼠血浆中异欧前胡素血药浓度变化,用DAS2.0药动学软件处理,计算其药物动力学参数。结果 异欧前胡素在大鼠体内过程符合二室模型特征,主要药动学参数为Tmax＝(1.6±0.000)h,Cmax＝(15.842±0.35)mg/L,AUC0-t＝(80.761±10.03)mg/(L?h),AUC0-∞＝(89.45±9.34)mg/(L?h),t1/2＝(5.101±0.24)h。结论 该方法适用于异欧前胡素的药物动力学研究。

【关键词】  白芷；异欧前胡素；高效液相色谱法；药动学参数；大鼠

    Abstract：Objective To establish a HPLC method for the determnation of serum concentration of isoimperatorin in rats and study pharmacokinetic characteristic of isoimperatorin in rat after drug admiaistraction. Method The concentrations of isoimperatorin in rats were determined after drug administration and the pharmacokinetic parameters of isoimperatorin were estimated by DAS2.0 computer program. Result The concentration-time profiles were fitted with open two compartment model system. The main pharmacokinetic parameters were as follows：Tmax ＝(1.6±0.000)h, Cmax ＝(15.842±0.35)mg/L, AUC0-t＝(80.761±10.03)mg/(L?h), AUC0-∞＝(89.45±9.34)mg/(L?h), t1/2＝(5.101±0.24)h. Conclusion The method is appropriate for the determination and pharmacokinetic study of isoimperatorin in rats after drug administration.
   
　　Key words：Radix angelicae dahuricae；isoimperatorin；HPLC；pharmacokinetic parameters；rat
 
    川白芷为川产道地药材,为伞形科植物杭白芷的根。白芷中香豆素类物质为重要的活性成分,其中异欧前胡素为重要成分之一。虽有异欧前胡素大鼠体内部分药物动力学特征的报道[1-2],但对血浆中异欧前胡素含量检测方法的报道较少,亦未见以异欧前胡素单体为研究对象的相关报道。本研究以川白芷提取物异欧前胡素单体为研究对象,通过建立相关的测定方法,确定了异欧前胡素在大鼠体内的主要药物动力学特征。

　　1  材料

　　1.1  仪器与试药

    瓦里安Prostar 210高效液相色谱仪；赛多利斯BP211DP (1/10万)电子天平；日本三洋超低温冰箱(-80 ℃)。白芷购于银发集团白芷GAP基地；异欧前胡素对照品购于四川省药品检验所。甲基叔丁基醚(MTBE)为色谱纯(美国TEDIA公司),水为双蒸水,甲醇为色谱纯,吐温-80为分析纯。