体外抑制作用的药物由人类细胞色素P450酶氧化反应催化1-aminobenzotriazole:比较与skf - 525 a和酮康唑。

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琼斯Emoto C, Murase年代,泽田师傅Y,公元前Iwasaki K

体外抑制作用的药物由人类细胞色素P450酶氧化反应催化1-aminobenzotriazole:比较与skf - 525 a和酮康唑。

药物金属底座Pharmacokinet。2003; 18 (5): 287 - 95。

PubMed ID

15618748 (在PubMed

]

文摘

1-Aminobenzotriazole (ABT)是广泛使用的非特异性抑制剂动物细胞色素P450 (CYP)。在目前的研究中,ABT的抑制作用是药物氧化反应催化研究由人类CYP亚型。这种抑制作用是与skf - 525 a相比,另一个非特异性抑制剂,和酮康唑,一种CYP3A的有效抑制剂。Bacurovirus-expressed重组人类CYP亚型被用作一种酶的来源。人类CYP亚型的具体活动有:非那西汀O-deethylation, CYP1A2;双氯芬酸4羟基化,CYP2C9;CYP2C19 S-mephenytoin 4羟基化,;CYP2D6 bufuralol 1 '羟基化,;chlorzoxazone 6-hydroxylation, CYP2E1;睾丸激素6 beta-hydroxylation、硝苯地平氧化和咪达唑仑1 ' CYP3A4的羟基化。 ABT inhibited both CYP1A2-dependent activity (Ki=330 microM) and CYP2E1-dependent activity (Ki=8.7 microM). In contrast, SKF-525A weakly inhibited CYP1A2-dependent activities (46% inhibition at 1200 microM) and CYP2E1-dependent activities (65% inhibition at 1000 microM). ABT exhibited the highest Ki value for CYP2C9-dependent diclofenac 4'-hydroxylation among those determined by this assay (Ki=3500 microM). Moreover, SKF-525A showed strong inhibition of CYP2D6-dependent bufuralol 1'-hydroxylation (Ki=0.043 microM). Ketoconazole inhibited all tested drug oxidations, however, its inhibitory effect on CYP1A2-dependent activities was very weak (50% inhibition at 120 microM). ABT, SKF-525A, and ketoconazole showed different selectivity and had a wide range of Ki values for the drug oxidations catalyzed by human CYP enzymes. Therefore, we conclude that inhibitory studies designed to predict the contribution of CYP enzymes to the metabolism of certain compounds should be performed using multiple CYP inhibitors, such as ABT, SKF-525A, and ketoconazole.

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药物酶

药物	酶	类	生物	药理作用	行动
酮康唑	细胞色素P450 2 c19	蛋白质	人类	未知的	抑制剂	细节
酮康唑	细胞色素P450 2 d6	蛋白质	人类	未知的	抑制剂	细节