【作者】 赵永红； 杨秀岭； 张志清； 刘建； 韩亚娟；

【Author】 ZHAO Yong-hong~(1*),YANG Xiu-ling~(1#),ZHANG Zhi-qing~1,LIU Jian~1,HAN Ya-juan~2 (1.Department of pharmacy,Second Hospital of Hebei Medical University,Hebei Shijiazhuang 050000,China;2.Faculty of Pharmacy,Hebei Medical University,Hebei Shijiazhuang 050017 China)

【机构】 河北医科大学第二医院药学部； 河北医科大学药学院；

【摘要】 目的:研究丁苯酞连续多次灌胃给药对大鼠CYP3A酶活性的影响。方法:40只Wistar大鼠随机分为四组。对照组灌胃给予橄榄油;实验组分为低、中、高3个剂量组,分别灌胃给予丁苯酞40mg·kg^-1、80mg·kg^-1、160 mg·kg^-1（以橄榄油溶解）。对照组和实验组均连续灌胃5天,于第6天尾静脉注射探针药物咪达唑仑(4mg·kg^-1)后由眼底静脉丛取血,高效液相色谱法测定血药浓度,以DAS 2.1.1药物动力学程序拟合药动学参数,以SPSS 18.0软件对组间各参数进行统计分析。结果:咪达唑仑在0.06～30μg·mL^-1内线性关系良好（r=0.9994）;日内、日间RSD<13%;绝对回收率为80.59%～96.52%。咪达唑仑单用及与低、中、高剂量丁苯酞合用比较,药动学参数AUC_0-t、AUC_0-∞、t_1/2、CL_Z、V_z没有显著性差别（P>0.05）。结论:丁苯酞对大鼠体内CYP3A酶活性没有影响。更多还原

【Abstract】 OBJECTIVE:To investigate the effect of butylphthalide on the enzymic activity of CYP3A in rats.METHODS:Forty Wistar rats were randomly divided into four groups.The control group were given intragastric ally to vegetable oil;the experimental group was divided into low, medium and high totally 3 dose groups,giving intragastrically butylphthalide 40 mg·kg^-1,80 mg·kg^-1, 160 mg·kg^-1（dissolved by vegetable oil）,respectively.The experimental group and the control group were orally for consecutive 5 days.Midazolam(4 mg·kg^-1) were given by tail intravenous on the sixth day,then taking blood from retinal vein plexus.The concentrations of Midazolam were determined by HPLC method.Pharmacokinetics parameters were calculated by DAS 2.1.1 pharmacokinetics programme.RESULTS:The linear range of midazolam was 0.06～30μg·mL^-1 （r=0.9994）.The RSD of intra-day and inter-day were all less than 13%,with an absolute recovery of 80.59%～96.52%.After midazolam was used alone and in combination with low,middle and high dose of butylphthalide,pharmacokinetic parameters of AUC（0-t）、AUC（O-∞）、CL_Z、V_Z and C_max had not significant difference（P>0.05）.CONCLUSION:Butylphthalide has no Effect on the enzymic activity of CYP3A in rats.更多还原