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溶剂对体外药物代谢的影响。

The effect of solvents on drug metabolism in vitro.

作者信息

Kawalek J C, Andrews A W

出版信息

Drug Metab Dispos. 1980 Nov-Dec;8(6):380-4.

PMID:6109604
Abstract

Nine water-miscible organic solvents, methanol, ethanol, acetone, ethoxyethanol, tetrahydrofuran, dioxane, dimethylformamide, acetonitrile, and dimethyl sulfoxide were each used with five commonly employed substrates of in vitro microsomal mixed-function oxidase assays containing liver 9,000g supernatant fractions from rats treated with phenobarbital or Aroclor 1254. When the metabolism of aminopyrine, aniline, 7-ethoxycoumarin, p-nitroanisole, and benzo[a]pyrene was determined in the presence of these solvents, varying degrees of stimulation and inhibition were observed. These effects were dependent on the substrate studied, the particular solvent incorporated into the assay, and the rat liver 9000g supernatant fraction used. These differential effects were also observed when 2-aminoanthracene was metabolically activated in the Ames Salmonella/mammalian-microsome mutagenicity test, but were not as dramatic when benzo[a]pyrene was tested.

摘要

九种与水混溶的有机溶剂,即甲醇、乙醇、丙酮、乙氧基乙醇、四氢呋喃、二氧六环、二甲基甲酰胺、乙腈和二甲基亚砜,分别与五种体外微粒体混合功能氧化酶测定中常用的底物一起使用,这些底物含有来自用苯巴比妥或多氯联苯混合物1254处理的大鼠的肝脏9000g上清液组分。当在这些溶剂存在下测定氨基比林、苯胺、7-乙氧基香豆素、对硝基苯甲醚和苯并[a]芘的代谢时,观察到了不同程度的刺激和抑制作用。这些效应取决于所研究的底物、测定中加入的特定溶剂以及所用的大鼠肝脏9000g上清液组分。当在埃姆斯沙门氏菌/哺乳动物微粒体诱变性试验中对2-氨基蒽进行代谢活化时,也观察到了这些差异效应,但在测试苯并[a]芘时,这些效应没有那么显著。

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