伊曲康唑对健康成人肝细胞微粒体细胞色素P450同工酶1A2、3A4活性的作用  

Effect of itraconazole on the activity of CYP450 1A2 and CYP450 3A4 of health adult human primary hepatocytes microsome

作　　者：刘振威[1] 胡卓汉 蔡映云[1] 

机构地区：[1]复旦大学附属中山医院呼吸病研究所,上海200032 [2]上海瑞德肝病研究所,上海200012

出　　处：《中国临床药学杂志》2006年第1期11-13,共3页Chinese Journal of Clinical Pharmacy

摘　　要：目的观察伊曲康唑对健康成人肝细胞微粒体细胞色素P450同工酶1A23、A4活性的作用,为临床上安全有效地联合用药提供实验依据。方法采用健康成人肝细胞微粒体,分为对照组和伊曲康唑处理组。处理组分别加入0.1、0.2、1.0、2.0、10.0、20.0 mg.L-1的伊曲康唑1mL,对照组仅加入培养液,孵育15 min后再加入CYP450同工酶1A2和3A4的相应底物(分别为非那西丁和睾酮)再孵育20min。反应终止后用高效液相色谱仪测量代谢产物(分别为对乙酰氨基酚与6β-羟基睾酮)的生成量代表1A2和3A4的活性。结果细胞色素P450同工酶1A2的相对活性百分比各处理组与对照组比较差异无显著性意义(P>0.05),而同工酶3A4的相对活性百分比随伊曲康唑质量浓度增加逐渐减小,各处理组与对照组比较差异均有显著性意义(P<0.05)。细胞色素P450同工酶3A4的相对活性百分比减小到对照组50%时(IC50)伊曲康唑的质量浓度为0.16 mg.L-1。结论伊曲康唑在临床应用血药质量浓度范围内,对健康成人肝细胞微粒体细胞色素P450同工酶1A2的活性无显著影响,然而对细胞色素P450同工酶3A4的活性有抑制作用。AIM To observe the effect of itraconazole on the activity of cytchrome P450（CYP） 1A2 and 3A4 of health adult human primary hepatocyte microsome. METHODS The health adult human primary hepatocyte microsome was randomly divided into control group and itraconazole groups with concentrations of 0,0.1,0.2, 1.0,2.0, 10.0, 20.0 mg·L^-1 respectively. After cultured with culture fluid for 15 min, substrates （ phenacetin for CYP1A2, testosterone for CYP3A4）were added and cultured for another 20 min. Then metabolites（acetaminophen and 6-testosterone）of them were measured with HPLC to assess the activities of CYP1A2 and 3A4. RESULTS There were no significant differences between itraconazole groups and control group in either quantity of acetaminophen or relative activity of CYP1A2 （ P 〉 0.05）. But both the quantity of 6-testosterone and the relative activity of CYP3A4 were diminished gradually following the increment of itraconazole＇s concentration. There were significant difference between every itraconazole groups and control groups in the quantity of 6-testosterone and the relative activity of CYP3A4 （ P 〈 0.05 ）. The IC50 of itraconazole for CYP450 3A4 was 0.16 mg·L^-1. CONCLUSION In the range of maximum clinical blood concentration, itraconazole can not inhibit the activity of CYP1A2 of health adult human primary hepatacyte microsome, but cought inhibit the activity of CYP3A4.

关 键 词：伊曲康唑 健康成人肝细胞微粒体 CYP1A2 CYP3A4 细胞色素P450 

分 类 号：R96[医药卫生—药理学]