体外抑制troglitazone及其代谢物对药物的影响人类细胞色素P450酶氧化活动:与吡格列酮和罗格列酮。

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山崎H,铃木M些K,岛田N、横井及其M T

体外抑制troglitazone及其代谢物对药物的影响人类细胞色素P450酶氧化活动:与吡格列酮和罗格列酮。

Xenobiotica。2000年1月,30 (1):61 - 70。

PubMed ID

10659951 (在PubMed

]

文摘

1。调查是一种新的口服抗糖尿病药的影响,troglitazone,其三个代谢物和抗糖尿病药候选人吡格列酮和罗格列酮对异型生物质氧化催化由九个重组人类细胞色素P450酶(P450或CYP)和由人类肝脏微粒体。2。Troglitazone (5 microM)显著地抑制CYP2C8-dependent紫杉醇6 alpha-hydroxylation CYP2C9-dependent S-warfarin 7-hydroxylation。另一方面,吡格列酮和罗格列酮(50 microM)稍微抑制这些异型生物质氧化活动由CYP2C酶催化的。3所示。的抑制潜力troglitazone(50%抑制浓度,IC50)大约是5 microM药物氧化反应催化CYP2C9和CYP2C8和大约20 microM活动分别CYP2C19和CYP3A4催化。troglitazone测试的三个代谢物,quinone-type代谢物(M3)是最有效的为CYP2C酶抑制剂,后跟一个硫酸共轭(M1);影响的葡糖苷酸(M2)非常薄弱。父的抑制性影响药物更有效的比代谢物。 Troglitazone and M3 inhibited P450 activities mainly through a competitive manner with Ki = 0.2-1.7 microM and 1.4-8.8 microM respectively. 4. In three human liver microsomes, troglitazone and its metabolites also inhibited paclitaxel 6alpha-hydroxylation, S-warfarin 7-hydroxylation, S-mephenytoin 4'-hydroxylation, and testosterone 6beta-hydroxylation with similar IC50, as observed for the recombinant P450 enzyme systems. 5. These results suggest that xenobiotic oxidations by P450 enzymes are more substantially affected by troglitazone and its metabolites than pioglitazone or rosiglitazone, and that drug interactions may be of much importance to understand the basis for the pharmacological and toxicological actions of this new oral antidiabetic drug.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
雷	细胞色素P450 2 c19	蛋白质	人类	未知的	底物 抑制剂	细节
Troglitazone	细胞色素P450 2 c19	蛋白质	人类	未知的	抑制剂	细节
Troglitazone	细胞色素P450 2 c8	蛋白质	人类	未知的	底物 抑制剂	细节
Troglitazone	细胞色素P450 2 c9	蛋白质	人类	未知的	底物 抑制剂	细节