Cocktail探针药物法评价灯盏花素对大鼠CYP450体内代谢活性的影响  

Influence of breviscapinum on CYP450 isoforms by Cocktail probe drugs method

作　　者：龚文奇[1,2] 梁晓光[3] 李芹[2] 刘洁[2] 汪云[2] 

机构地区：[1]天津市武清区王庆坨医院护理部,天津301713 [2]天津医科大学基础医学院药理教研室,天津300070 [3]卫生部北京医院急诊科,北京100730

出　　处：《中国临床药理学杂志》2012年第6期440-443,共4页The Chinese Journal of Clinical Pharmacology

基　　金：天津市自然科学基金重点基金资助项目(09JCZDJC21500);高等学校博士学科点专项科研基金资助项目(新教师基金)资助课题(20091202120012)

摘　　要：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 influence of breviscapinum on the activities of CYP1A2,CYP2C9,CYP2E1 and CYP2D6 by cocktail probe drugs in rats.Methods The rats were randomly divided into three groups,control group,low dose group and high dose group.The rats in the low dose group and high dose group were treated with intravenous breviscapinum through caudal veins at the dose of 1.8,5.4 mg·kg-1 once a day for 14 days respectively.The rats in the control group were injected with normal saline.On the 15th day,all rats in each group were injected with cocktail probes.The plasma concentrations of the different probe drugs were determined by HPLC and the main pharmacokinetic parameters were calculated.Results Compared with the control group,the AUC and t1/2 of metoprolol were significantly increased and the CL of metoprolol was significantly decreased in high dose group（P0.05）.In low dose group,the pharmacokinetic parameters of metoprolol had the similar trend with high dose group,but it was not significantly different with those of the control group.There were no significant differences for the pharmacokinetic parameters of caffeine,chlorzoxazone and tolbutamide among these three groups.Conclusion High dose intravenous breviscapinum powder can inhibit the activity of CYP2D6,but has no influence on the activities of CYP1A2,CYP2C9 and CYP2E1.

关 键 词：COCKTAIL探针药物法 CYP1A2 CYP2C9 CYP2E1 CYP2D6 灯盏花素 

分 类 号：R285.5[医药卫生—中药学] R969.1[医药卫生—中医学]