参与CYP2C9和UGT2B7 zaltoprofen的新陈代谢,非甾体类抗炎药,其缺乏临床重大CYP抑制的潜力。

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Furuta年代,Akagawa N, Kamada E, Hiyama,川端康成Y, Kowata N,稻叶型,马修斯,大厅,Kurimoto T

参与CYP2C9和UGT2B7 zaltoprofen的新陈代谢,非甾体类抗炎药,其缺乏临床重大CYP抑制的潜力。

Br中国新药杂志。2002年9月,54 (3):295 - 303。

PubMed ID

12236850 (在PubMed

]

文摘

目的:识别细胞色素P450 (CYP)和UDP-glucuronosyltransferase (UGT)亚型负责的形成主要代谢物zaltoprofen (s),并预测可能的药物相互作用通过调查CYP亚型体外的抑制。方法:体外代谢研究了zaltoprofen使用重组CYP和UGT同种型cdna表达系统。选择性同种型抑制剂zaltoprofen代谢的影响进行了研究使用人类肝脏微粒体。的抑制效应zaltoprofen选择性探针底物的代谢CYP1A2, CYP2C9, CYP2C19、CYP2D6、CYP2E1和CYP3A4也决定在人类肝脏微粒体。结果:Zaltoprofen被CYP2C9和UGT2B7广泛代谢。CYP2C9促成sulphoxidation但不是zaltoprofen的羟基化。在人肝微粒体代谢研究中,zaltoprofen代谢被sulphaphenazole明显抑制,CYP2C9的选择性抑制剂。在药物相互作用的研究中,可以忽略的抑制(< 15%)的活动CYP1A2, CYP2C19、CYP2D6、CYP2E1和CYP3A4明显在5微g毫升(1),最大血浆浓度在人类观察到的口服80毫克zaltoprofen平板电脑。然而,zaltoprofen抑制CYP2C9 26% 5微g毫升(1)。在较高的浓度,zaltoprofen产生一些抑制CYP2C9 (IC50微g = 19.2毫升(1); 64.4 micro m) and CYP3A4 (IC50 = 53.9 micro g ml(-1); 181 micro m). The free drug concentrations in plasma (0.02 micro g ml(-1), 67.0 nm) at the Cmax of the clinically effective doses are much lower than the IC50 values corrected for the nonspecific binding ratio of zaltoprofen to microsomal protein (15.5 micro g ml(-1) for CYP3A4, 49.5 micro g ml(-1) for CYP3A4). Furthermore, the maximum free drug concentrations in the hepatic intracellular was calculated to be 0.068 micro g ml(-1) and the increase in the AUC in the presence of zaltoprofen was estimated to be only 0.4% for CYP2C9 substrates and 0.1% for CYP3A4 substrates, respectively. CONCLUSIONS: Zaltoprofen is predominantly metabolized by CYP2C9 and UGT2B7, and is considered unlikely to cause significant drug interactions in vivo when coadministered with CYP substrates at clinically effective doses.

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
Zaltoprofen	细胞色素P450 2 c9	蛋白质	人类	未知的	底物	细节