黄芪甲苷通过抑制大鼠体内CYP1A2酶活性影响药物相互作用

目的研究黄芪甲苷对大鼠体内CYP1A2酶活性的影响,阐明由CYP1A2酶所引发的药物相互作用可能性。方法采用色谱柱为waters-symmetry C18柱(250 mm×4.6 mm I.D.,5μm);流动相为甲醇和水(体积比17∶83);检测波长=274 nm;柱温=30℃;流速=1 ml/min的色谱条件。7只SD大鼠随机分为2组,实验组3只预给予黄芪甲苷1周,对照组4只给予0.1%DMSO水溶液,第8天分别给予茶碱,通过高效液相色谱法测定探针药物茶碱的血药浓度,比较2组的动力学参数的差异来考察黄芪甲苷对CYP1A2酶活性的影响。结果茶碱、内标对乙酰氨基酚二者分离良好且无内源性干扰,茶碱的最低检测限80 nmol/L,线性范围0.2～50μmol/L,日内日间精密度均小于10%,提取回收率大于91%,实验组的动力学参数药物浓度-时间曲线下面积AUC(0-∞)(131.16±3.22)明显高于对照组(97.51±6.40),而体内总体清除常数CL/F(0.12±0.01)明显低于对照组(0.17±0.02)(P<0.05)。结论黄芪甲苷对大鼠体内CYP1A2酶活性有明显的抑制作用,临床用药中应尽量避免与由CYP1A2所代谢的药物联合应用。

Astragaloside Ⅳ exerts drug interactions via inhibiting CYP1A2 activity in rats

Objective To determine the effect of astragaloside Ⅳ(AGS-Ⅳ) on the activity of CYP1A2 in rats to elucidate the possibility CYP1A2-induced interactions of drugs.Methods Analysis of theophylline,and acetamidophenol(internal standard) was achieved using waters C18 column(250 mm×4.6 mm×5 μm) and a mobile phase consisted of methanol-water(17∶83,v/v) was delivered at a flow rate of 1.0 ml/min at 30 ℃ at a wavelength of 274 nm.Seven rats were divided into 2 groups by simple random sampling.Three rats were intravenously treated with AGS-Ⅳ(3 mg/kg),and the left 4 rats were intravenously administered with an equivalent volume of 0.1% DMSO vehicle once a day for a week.On the eighth day,all of the rats were intragastrically administered theophylline.The concentration of theophylline in the plasma was determined by high performance liquid chromatography(HPLC).The distinction of pharmacokinetic parameters was compared to investigate the effect of AGS-Ⅳ on the activity of CYP1A2.Results Theophylline and acetamidophenol were separated well,the detection limit of theophylline was 80 nmol/L,and the linear rang of our method was 0.2 to 50 μmol/L.The intra-day and inter-day relative standard deviations were both less than 10%,and the recoveries were more than 91.The main pharmacokinetic parameters of area under the concentration-time cure(AUC) of theophylline were higher than control groups(131.16±3.22 vs 97.51±6.40).The apparent oral total body clearance value(CL/F) of test group and control group were 0.12±0.01 and 0.17±0.02 respectively,with the former obviously lower than the latter(P<0.05).Conclusion AGS-Ⅳ exerts obvious inhibitory effect on CYP1A2 activity in rats,so its should be cautious to co-administer with drugs metabolized by CYP1A2.