Cocktail法考察益气复脉对大鼠CYP450酶亚型活性的影响  

Evaluation on the influence of Yiqifumai injection on the activities of cytochrome P450 enzymes in rats by cocktail probe approach

作　　者：李挺洋 李潇[2,3] 周鸿杰[2,3] 褚扬[2,3] 周大铮[3,4] 王相阳[2,3] 李伟[2,3,5] 杨劲[1] 鞠爱春 刘昌孝[3,6] 

机构地区：[1]中国药科大学药物代谢研究中心,南京210009 [2]天士力研究院,天津300410 [3]天士力制药集团股份有限公司创新中药关键技术国家重点实验室,天津300410 [4]天津天士力之骄药业有限公司,天津市中药注射剂安全性评价企业重点实验室,天津300410 [5]中国中医科学院中药资源中心,北京100700 [6]天津药物研究院释药技术与药动学国家重点实验室,天津300193

出　　处：《中国新药杂志》2016年第9期1046-1051,共6页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项(2013ZX09602202)

摘　　要：目的:研究注射用益气复脉(冻干)对大鼠3种细胞色素P450酶亚型1A2,3A和2E1体内代谢活性的影响。方法:将大鼠随机分为3组,低、高剂量组和空白对照组。低和高剂量组分别尾静脉注射益气复脉542和1 084 mg·kg-1·d-1,空白对照组给予等体积0.9%Na Cl溶液,连续7 d。d 8灌胃(ig)给予探针药混合溶液,用UPLC检测各探针的血药浓度。结果:与空白对照组相比,高剂量组氯唑沙宗的清除率(CL/F)升高,差异有统计学意义(P<0.05)。各组茶碱和氨苯砜的主要药动学参数均无显著差异。结论:高剂量益气复脉对大鼠CYP2E1有一定的诱导作用,而对CYP1A2和3A并无显著性影响。Objective： To study the influence of Yiqifumai injection on the activities of CYP1A2,CYP3 A,and CYP2E1 in rats by cocktail probe drugs approach. Methods： The rats were randomly divided into low dose group,high dose group,and control group. The rats in the low and high dose groups were treated with Yiqifumai injection via the caudal vein at the dose of 542 and 1 084 mg·kg^- 1·d^- 1for 7 days,respectively. The rats in the control group were injected with equal volume of normal saline. On the 8th day,all the rats were administered withprobe drugs. The blood concentrations of probe drugs were determined by UPLC. Results： Compared with the control group,the clearance（ CL） of chlorzoxazone in the high dose group increased（ P〈0. 05）. There were no significant differences for the main pharmacokinetics parameters of theophylline and dapsone among the three groups.Conclusion： High dose Yiqifumai injection can induce the activity of CYP2E1 slightly,while it has no significant influence on the activities of CYP1A2 and 3A.

关 键 词：益气复脉 CYP1A2 CYP3A CYP2E1 COCKTAIL探针药物法 UPLC 

分 类 号：R96[医药卫生—药理学] R972[医药卫生—药学]