探针药物法评价丁苯酞对大鼠体内CYP3A酶活性的影响

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4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40、80、160 mg·kg^-1（以橄榄油溶解）。对照组和实验组均连续灌胃5 d,于第6日尾静脉注射探针药物咪达唑仑（4 mg·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SPSS18.0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=0.999 4）;日内、日间RSD〈13%;绝对回收率为80.59%～96.5%。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AUC0～t、AUC0～∞、t1/2、CLZ、VZ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。

Probe drugs for detecting effect of butylphthalide on CYP3A in rats

Objective To investigate the effect of butylphthalide on the enzymic activity of CYP3A in rats. Methods Forty Wistar rats were randomly divided into 4 groups. The control group was intragastrically given vegetable oil; and the experimental group was subdivided into low, medium and high dose groups, intragastrically given butylphthalide 40, 80, and 160 mg · kg- 1（dissolved by vegetable oil）, respectively. The experimental group and the control group were gavage dose for 5 days consecutively. Midazolam（4 mg · kg- 1） was given by tail intravenously on the 6th day, and then blood was taken from the retinal vein plexus. The concentrations of midazolam were determined by HPLC method. Pharmacokinetic parameters were calculated by DAS 2.1.1 pharmacokinetics program. Results The linear range of midazolam was 0.06- 30 μg · mL- 1（r = 0.999 4）. The RSDs of intra-day and inter-day were all less than 13%, with an absolute recovery of 80.59%- 96.5%. When midazolam was used alone or in combination with low, middle and high dose of butylphthalide, the pharmacokinetic parameters AUC0 ～ t, AUC0 ～∞, CLZ, and VZ had no significant difference（P〈0.05）. Conclusion Butylphthalide has no effect on the enzymic activity of CYP3A in rats.