由人类肝脏代谢zaleplon:参与醛氧化酶的证据。
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BG湖,球,花王J, Renwick AB,价格RJ Scatina农协
由人类肝脏代谢zaleplon:参与醛氧化酶的证据。
Xenobiotica。2002年10月,32 (10):835 - 47。
- PubMed ID
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12419014 (在PubMed]
- 文摘
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1。的新陈代谢Zaleplon (cl - 284846;ZAL)研究了在展示人类肝脏切片和肝细胞溶质的准备。2。人类的肝脏切片代谢ZAL许多产品,包括5-oxo-ZAL (M2), N-desethyl-5-oxo-ZAL (M1)和N-desethyl-ZAL (DZAL),后者代谢物被认为是由CYP3A形式。3所示。人类肝细胞溶质准备催化新陈代谢ZAL M2。动力学分析的三个细胞溶质准备透露的意思是(+ / - SEM) K (m)和V (max) 93 + / - 18毫米和317 + / - 241 pmol /分钟/毫克蛋白,分别。4所示。使用16个人人类肝细胞溶质准备33倍的代谢变化80微ZAL M2是观察。 Correlations were observed between M2 formation and the metabolism of the aldehyde oxidase substrates phenanthridine (r(2) = 0.774) and phthalazine (r(2) = 0.460). 5. The metabolism of 80 micro M ZAL to M2 in liver cytosol preparations was markedly inhibited by the aldehyde oxidase inhibitors chlorpromazine, promethazine, hydralazine and menadione. Additional kinetic analysis suggested that chlorpromazine and promethazine were non-competitive inhibitors of M2 formation with K(i) of 2.3 and 1.9 micro M, respectively. ZAL metabolism to M2 was also inhibited by cimetidine. 6. Incubations conducted with human liver cytosol and H(2)(18)O demonstrated that the oxygen atom incorporated into ZAL and DZAL to form M2 and M1, respectively, was derived from water and not from molecular oxygen. 7. In summary, by correlation analysis, chemical inhibition and H(2)(18)O incorporation studies, ZAL metabolism to M2 in human liver appears to be catalysed by aldehyde oxidase. With human liver slices, ZAL was metabolized to products dependent on both aldehyde oxidase and CYP3A forms.