氢溴酸槟榔碱对人肝CYP450酶的体外影响  

Effect of arecoline hydrobromide on human hepatic cytochrome P450 activity in vitro

作　　者：肖润梅 肖晨曦 Run-mei Xiao;Chen-xi Xiao(Department of Pharmacy, Hubei Provincial Hospital of Integrated Chinese and Western Medicine,Wuhan, Hubei 430015, China;College of Life Sciences, Wuhan University,Wuhan, Hubei 430072, China)

机构地区：[1]湖北省中西医结合医院药剂科,湖北武汉430015 [2]武汉大学生命科学院,湖北武汉430072

出　　处：《中国现代医学杂志》2018年第8期30-34,共5页China Journal of Modern Medicine

摘　　要：目的采用液质联用法结合特异性探针技术,研究氢溴酸槟榔碱(AH)对人肝微粒体(HLM)中细胞色素P450(CYP450)亚型酶的体外影响。方法将CYP1A2、2E1、3A4、2C9、2D6、2B6的探针底物分别在0~160μmol/L AH的HLM中温孵,高效液相法测定CYP1A2、2E1、3A4、2C9的酶活性;高效液相色谱-串联质谱仪测定CYP2D6、2B6的酶活性。结果 AH对HLM中CYP2D6、2B6、2E1、2C9的酶活性有轻微抑制作用,且随AH浓度的升高而增强。当AH为160μmol/L时,对CYP2D6、2B6、2E1、2C9酶活性的抑制率分别为36.2%、38.3%、35.0%和35.4%。结论槟榔嗜好者使用CYP1A2、2E1、3A4、2C9、2D6、2B6 6个CYP450酶的底物药物时,其代谢相互作用的风险仍不可忽视。Objective To observe the influences of arecoline hydrobromide(AH)on human hepatic cytochrome P450activity in vitro by high performance liquid chromatography-mass spectrometry(HPLC-MS)and a cocktail probe substrates method.Methods In this study,six probe substrates of CYP1A2,2E1,3A4,2C9,2D6and2B6were simultaneously incubated with human liver microsome(HLM)and AH(0-160μmol/L).The activity of CYP1A2,2E1,3A4and2C9was determined by HPLC,and the activity of CYP2D6and2B6was determined by HPLC-MS.Results The activity of CYP2D6,2B6,2E1and2C9in HLM was slightly inhibited by AH,which was concentration-dependent.When the AH concentration was160μmol/L,the inhibitory rates of the activity of CYP2D6,2B6,2E1and2C9in HLM were36.2%,38.3%,35.0%and35.4%,respectively.Conclusions The risk of metabolic interaction should not be neglected when the substrate drugs of the six kinds of cytochrome P450isoforms are administered in betelnut addicts.

关 键 词：高效液相 细胞色素P450 人肝微粒体 特异性探针底物 氢溴酸槟榔碱 

分 类 号：R285.5[医药卫生—中药学]