由人类肝微粒体代谢Zaleplon细胞色素P450亚型。

文章的细节

引用

复制到剪贴板

Renwick AB, Mistry H,球,沃尔特斯DG,花王J, BG湖

由人类肝微粒体代谢Zaleplon细胞色素P450亚型。

Xenobiotica。1998年4月28日(4):337 - 48。doi: 10.1080 / 004982598239452。

PubMed ID

9604298 (在PubMed

]

文摘

1。的新陈代谢Zaleplon (cl - 284846;ZAL)研究了在人类肝微粒体准备和cDNA-expressed人类细胞色素P450 (CYP)亚型。2。人类肝微粒体催化了NADPH-dependent N-deethylation的ZAL DZAL (cl - 284859),而不是两个已知的体内代谢物,即M1 (cl - 345644)和M2 (cl - 345905)。反曲的动能情节被观察到ZAL deethylation表明积极的协调。3所示。的新陈代谢ZAL DZAL决心在24人肝微粒体准备银行的特征。良好的相关性(r2 = 0.734 - -0.937)观察与咖啡因8-hydroxylase安定3-hydroxylase,右美沙芬N-demethylase和睾酮2β- 6β- 15 beta-hydroxylase活动,这些都是催化了CYP3A亚型。相比之下,可怜的相关性(r2 = 0.152 - -0.428)观察酶标记CYP1A2,体内CYP2A6基因表现,CYP2C9/10, CYP2D6、CYP2E1和CYP4A9/11。 4. The metabolism of ZAL to DZAL in human liver microsomes was inhibited to 6-15% of control by 5-50 microM of the mechanism-based CYP3A inhibitor troleandomycin. Whereas some inhibition of DZAL formation was observed in the presence of 200 microM diethyldithiocarbamate, 5-50 microM furafylline, 2-20 microM sulphaphenazole, 50-500 microM S-mephenytoin and 1-10 microM quinidine had little effect. 5. Using human B-lymphoblastoid cell microsomes containing cDNA-expressed CYP isoforms, ZAL was metabolized to DZAL by CYP3A4, hut not to any great extent by CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. 6. In contrast with ZAL, the NADPH-dependent N-deethylation of M2 to M1 proceeded at only a very low rate with both human liver microsomes and cDNA-expressed CYP3A4. 7. In summary, by correlation analysis, chemical inhibition studies and the use of cDNA-expressed CYPs, ZAL N-deethylation to DZAL in human liver appears to be catalysed by CYP3A isoforms.

beplay体育安全吗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
Zaleplon	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节