Paterson P, Fry J R, Horner S A
Xenobiotica. 1984 Nov;14(11):849-59. doi: 10.3109/00498258409151483.
Pretreatment of rats with phenobarbitone increased hepatic microsomal 7-methoxy-and 7-ethoxy-coumarin O-dealkylase activities. Pretreatment with beta-naphthoflavone increased only the 7-ethoxycoumarin O-dealkylase activity. The addition of metyrapone in vitro inhibited the O-dealkylations to different extents. Similar results were obtained with diphenyloxazole and ethanol. These results are taken to indicate that different forms of cytochrome P-450 are involved in the O-dealkylation of these two substrates. The pattern of metabolism (Phase I and Phase II) of each alkoxycoumarin in rat isolated hepatocytes was very similar. The sulphate conjugate was the major metabolite produced, the amount of which approached a plateau as the rate of O-dealkylation increased. It is concluded that the type of cytochrome P-450 involved in the initial Phase I metabolism does not influence the subsequent pattern of conjugation.
用苯巴比妥预处理大鼠可增加肝脏微粒体7-甲氧基香豆素和7-乙氧基香豆素O-脱烷基酶的活性。用β-萘黄酮预处理仅增加7-乙氧基香豆素O-脱烷基酶的活性。体外添加甲吡酮不同程度地抑制了O-脱烷基反应。二苯恶唑和乙醇也得到了类似的结果。这些结果表明不同形式的细胞色素P-450参与了这两种底物的O-脱烷基反应。大鼠离体肝细胞中每种烷氧基香豆素的代谢模式（I相和II相）非常相似。硫酸酯结合物是主要产生的代谢产物，随着O-脱烷基反应速率的增加，其生成量趋于平稳。结论是参与初始I相代谢的细胞色素P-450类型不影响随后的结合模式。
