鸡尾酒法评价石蒜对大鼠细胞色素P450酶活性的影响  

Effect of Lycoris Radiata on CYP450 Enzyme Activity in Rats by Cocktail Method

作　　者：李剑波[1] 陈毅芳[1] 张玮[1] 方俊杰 祝大部 鲁迎 谢明华[1] LI Jianbo;CHEN Yifang;ZHANG Wei;FANG Junjie;ZHU Dabu;LU Ying;XIE Minghua(The First People's Hospital of Yuhang District,Hangzhou 311100,China)

机构地区：[1]杭州市余杭区第一人民医院,杭州311100

出　　处：《中国现代应用药学》2021年第20期2501-2504,共4页Chinese Journal of Modern Applied Pharmacy

基　　金：杭州市卫生科技计划项目(0020190325);浙江省医学会临床科研基金项目(2018ZYC-A52);浙江省药学会医院药学专项科研资助项目(2018ZYY12)。

摘　　要：目的运用鸡尾酒法评价石蒜对细胞色素P450酶活性的影响。方法将大鼠随机分为对照组和石蒜低、高剂量组。对照组给予生理盐水,石蒜低、高剂量组大鼠灌胃给药0.5,1.0 g·kg^(-1)石蒜,连续给药15 d。然后第16天给予探针药物,UPLC-MS/MS检测探针药浓度。结果与对照组对比,石蒜低剂量组和高剂量组的安非他酮AUC_((0-t))、C_(max)都显著升高(P<0.05),CL_(z/F)显著降低(P<0.05)。与对照组对比,石蒜高剂量组的美托洛尔、咪达唑仑和非那西丁AUC_((0-t))显著降低(P<0.05)、CL_(z/F)显著升高(P<0.05),而低剂量组与对照组比较差异无统计学意义。与对照组对比,石蒜组的甲苯磺丁脲AUC_((0-t))、CL_(z/F)差异无统计学意义,C_(max)显著降低(P<0.05)。结论石蒜能抑制大鼠CYP2B1酶活性,诱导大鼠CYP2D1、CYP3A2和CYP1A2酶活性,稍有诱导大鼠CYP2C11酶活性的作用。OBJECTIVE To evaluate the effect of Lycoris radiata on cytochrome P450 enzyme activity using the cocktail method.METHODS Rats were randomly divided into three groups:the control group,low and high dose of Lycoris radiata group.The control group was given physiological saline,and the rats in the low and high dose of Lycoris radiata group were intragastrically administrated 0.5,1.0 g·kg^(-1) of Lycoris radiata for 15 d.Then on the 16th day,probe drugs were administrated by gavage,and the concentration of probe drugs was determined by UPLC-MS/MS.RESULTS Compared with the control group,the AUC_((0-t)) and C_(max) of bupropion in the low and high dose of Lycoris radiata group increased(P<0.05)and the CL_(z/F)decreased(P<0.05).Compared with the control group,the AUC_((0-t)) of metoprolol,midazolam,and phenacetin in the high dose Lycoris radiata group decreased(P<0.05),and CL_(z/F) increased(P<0.05),while there was no statistical difference between the low dose Lycoris radiata group and the control group.Compared with the control group,the AUC_((0-t)) and CL_(z/F) of tolbutamide in the Lycoris radiata group were not statistically different,but the C_(max) of the Lycoris radiata group decreased(P<0.05).CONCLUSION Lycoris radiata can inhibit CYP2B1 enzyme activity in rats,induce CYP2D1,CYP3A2 and CYP1A2 enzyme activities in rats,and slightly induce CYP2C11 enzyme activity in rats.

关 键 词：石蒜 CYP2B1 CYP2D1 CYP3A2 CYP1A2 UPLC-MS/MS 

分 类 号：R285.5[医药卫生—中药学]