论文部分内容阅读
目的用Cocktail探针药物法研究灯盏花素对大鼠CYP1A2、CYP2C9、CYP2E1和CYP2D6体内代谢活性的影响。方法将大鼠随机分为3组,空白对照组、低剂量组和高剂量组。低剂量组和高剂量组分别尾静脉给予灯盏花素粉针剂1.8,5.4 mg.kg-1.d-1,空白对照组给予生理盐水,共14 d。各组分别于第15 d注射Cocktail探针溶液,用HPLC检测各探针药物的血药浓度,用DAS2.0计算药代动力学参数,评价相应的CYP450亚型的体内代谢活性。结果高剂量组美托洛尔的AUC和t1/2显著高于空白对照组,CL显著低于空白对照组(P<0.05)。低剂量组美托洛尔虽然也有相同趋势,但差异无统计学意义(P>0.05)。各组咖啡因、氯唑沙宗和甲苯磺丁脲的主要药代动力学参数均无显著差异(P>0.05)。结论高剂量灯盏花素粉针剂可明显抑制大鼠CYP2D6的体内代谢活性,而对CYP1A2、CYP2E1和CYP2C9无显著性影响。
Objective To study the effect of breviscapine on the metabolic activity of CYP1A2, CYP2C9, CYP2E1 and CYP2D6 in rats by Cocktail probe method. Methods The rats were randomly divided into three groups, blank control group, low dose group and high dose group. Low-dose group and high-dose group were given breviscapine injection 1.8, 5.4 mg.kg-1.d-1 tail vein, saline control group, a total of 14 d. Cocktail probe solution was injected into each group on the 15th day, and the plasma concentration of each probe drug was measured by HPLC. The pharmacokinetic parameters were calculated by DAS2.0 to evaluate the in vivo metabolic activity of the corresponding CYP450 subtypes. Results The AUC and t1 / 2 of metoprolol in the high-dose group were significantly higher than those in the blank control group, and CL was significantly lower than that in the blank control group (P <0.05). Metoprolol in the low-dose group had the same trend, but the difference was not statistically significant (P> 0.05). There was no significant difference in the main pharmacokinetic parameters between caffeine, chlorzoxazone and tolbutamide (P> 0.05). Conclusion High-dose Breviscapine injection can significantly inhibit the metabolism activity of CYP2D6 in rats, but has no significant effect on CYP1A2, CYP2E1 and CYP2C9.