厚朴提取物对人肝微粒5种药物代谢酶活性的影响  

THE EFFECTS OF HOUPO EXTRACTIVE ON DRUG METABOLISM ENZYMES OF HUMAN LIVER MICROSOME

作　　者：高雯 徐文[2] 龚伟玲[2] 曹志红[2] 马敏[2] 孙勇[1] 

机构地区：[1]青岛大学医学院药学院,山东青岛266021 [2]青岛大学医学院附属医院药剂科,山东青岛266021

出　　处：《青岛大学医学院学报》2014年第2期127-129,132,共4页Acta Academiae Medicinae Qingdao Universitatis

基　　金：青岛市民生计划项目(13-1-3-32-nsh)

摘　　要：目的观察厚朴提取物对人体肝微粒中5种主要药物代谢酶CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4活性的影响,为临床中西药联用提供理论依据。方法采用人体肝微粒体外孵育方法,以非那西丁、甲苯磺定脲、美芬妥因、氢溴酸右美沙芬和咪达唑仑作为CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4的探针药物,采用液相色谱-质谱联用检测探针药物代谢产物生成速率,通过与空白组探针药物代谢产物生成速率比较,计算厚朴提取物对这5种酶活性是否具有影响。结果厚朴提取物在10mg/L浓度下,对CYP2C9和CYP2C19具有明显抑制作用,分别抑制了(94.9±0.4)%、(90.3±0.3)%的活性;对CYP1A2、CYP2D6和CYP3A4没有明显抑制作用;经对数拟合计算,得出CYP2C9和CYP2C19的IC50值分别为0.470、0.717mg/L。结论厚朴提取物对CYP2C9和CYP2C19的活性有较强的抑制作用,若与其他药物同时服用,可能会引起药物之间的相互作用,临床用药需谨慎。Objective To observe the effects of Houpo extractive on five main drug metabolism enzymes （CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4） of human liver microsome, and provide theoretical basis for clinical combined use of traditional Chinese medicine and western medicine. Methods Human liver microsome incubation experiment was carried out to assay the extractive on the catalytic activities of the enzymes. Phenacetin, tolbutamide, S-mephenytoin, dextromethorphane and midazolam were used as the substrates of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, respectively. After incubation, the metabolites of the substrate were quantified by HPLC-MS/MS method. The inhibitions of five main drug metabolism enzymes were calculated by comparing the formation velocities of metaholites with or without Houpo extractive. Results Under 10 mg/ L, Houpo had a strong inhibitory effect on the activity of CYP2C9 and CYP2C19, being （94.9±0.38） % and （90.3±0.26） %, respectively, Houpo showed no significant inhibitory effects on the activity of CYP1A2, CYP2D6 and CYP3A4. The ICso values of CYP2C9 and CYP2C19 were 0.470 mg/L and 0.717 mg/L, respectively, by logarithmic function. Conclusion Houpo extractive has a strong inhibitory effect on the activity of CYP2C9 and CYP2C19, taking it with other drugs should be careful to avoid potential problems such as drug interactions.

关 键 词：厚朴提取物 微粒体 肝 药物代谢酶 抑制 化学性 

分 类 号：R969.2[医药卫生—药理学]