KETOCONAZOLE AND SULFAPHENAZOLE AS THE RESPECTIVE SELECTIVE INHIBITORS OF P4503A AND 2C9
KETOCONAZOLE AND SULFAPHENAZOLE AS THE RESPECTIVE SELECTIVE INHIBITORS OF P4503A AND 2C9
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DOI：
10.3109/00498259509061850
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发表时间：
1995-03-01
期刊：
影响因子：
1.8
通讯作者：
CHENERY, RJ
中科院分区：
文献类型：
--
作者：
BALDWIN, SJ;BLOOMER, JC;CHENERY, RJ
1.以人肝微粒体为实验材料，研究了酮康唑和磺苯唑对特异性P450酶(1A2、2A6、2B6、2C9/8、2C19、2D6、2E1、3A和4A)的抑制作用。酮康唑对环孢素氧化酶和睾酮6β-羟基酶活性有抑制作用，其IC50‘S分别为0.19和0.22mU/L。酮康唑对所考察的其他P450活性的抑制明显较小，从IC50的S来看，至少高了一个数量级。磺胺苯唑对甲苯磺丁胺羟基化酶活性有抑制作用，在含100 mU甲苯基丁胺的孵育条件下，其IC50平均值为0.8 mU M。磺胺苯唑(浓度高达100 mU M)对所研究的其他酶活性没有表现出任何明显的抑制作用。酮康唑和磺苯唑分别是P4503A和2C9的选择性抑制剂。1 mU M的酮康唑和10 mU M的磺胺苯唑可分别确定P4503A和2C9参与人肝微粒体的氧化反应。
1. The potential of ketoconazole and sulphaphenazole to inhibit specific P450 enzyme activities (1A2, 2A6, 2B6, 2C9/8, 2C19, 2D6, 2E1, 3A and 4A) was investigated using human liver microsomes.2. Ketoconazole demonstrated an inhibitory effect on cyclosporine oxidase and testosterone 6 beta-hydroxylase activities, with mean IC50's of 0.19 and 0.22 mu M respectively. Ketoconazole inhibition of the other P450 activities investigated was significantly less, as illustrated by IC50's of at least a magnitude higher.3. Sulphaphenazole was shown to have an inhibitory effect on tolbutamide hydroxylase activity, with a mean IC50 of 0.8 mu M in incubations containing 100 mu M tolbutamide. Sulphaphenazole (at concentrations of up to 100 mu M) did not exhibit any significant inhibition of the other enzyme activities investigated.4. Ketoconazole and sulphaphenazole are the respective selective inhibitors of P4503A and 2C9. Ketoconazole at 1 mu M and sulphaphenazole at 10 mu M can be used to establish the involvement of P4503A and 2C9 respectively in oxidative reactions in human liver microsomes.