Rice S A, Talcott R E
Drug Metab Dispos. 1979 Sep-Oct;7(5):260-2.
The hepatic microsomal content of cytochromes P-450 and b5, the defluorination rates of four volatile fluorinated ether anesthetics, and the activities of selected mixed-function oxidases were compared following administration of either isoniazid, phenobarbital, beta-naphthoflavone, or saline to male Fischer 344 rats. Isoniazid treatment significantly increased the rate of metabolism of p-nitroanisole, ethoxyresorufin, aniline, methoxyflurane, enflurane, isoflurane, and sevoflurane, significantly decreased the rate of metabolism of aminopyrine, and did not alter the activity of NADPH-cytochrome c reductase or the microsomal contents of cytochromes b5 and P-450 per mg of microsomal protein. The pattern of catalytic activities associated with isoniazid induction did not resemble that of either phenobarbital or beta-naphthoflavone induction. Furthermore, isoniazid treatment resulted in a shift in the (reduced cytochrome P-450 plus CO) absorption maximum from 450 to 451 nm. This shift in absorption, coupled with the observation that the total microsomal cytochrome P-450 content is not elevated, suggests that there is an increased production of one species of cytochrome P-450. The great enhancement of enflurane defluorination following isoniazid treatment was of particular interest because other enzyme-inducing agents, including phenobarbital, 3-methylcholanthrene, phenytoin, and beta-naphthoflavone, have not been found to increase enflurane defluorination to a clinically significant level.
给雄性Fischer 344大鼠分别给予异烟肼、苯巴比妥、β-萘黄酮或生理盐水后，比较了细胞色素P-450和b5的肝微粒体含量、四种挥发性含氟醚类麻醉剂的脱氟速率以及所选混合功能氧化酶的活性。异烟肼处理显著提高了对硝基苯甲醚、乙氧芴香豆素、苯胺、甲氧氟烷、恩氟烷、异氟烷和七氟烷的代谢速率，显著降低了氨基比林的代谢速率，并且未改变每毫克微粒体蛋白中NADPH-细胞色素c还原酶的活性或细胞色素b5和P-450的微粒体含量。与异烟肼诱导相关的催化活性模式与苯巴比妥或β-萘黄酮诱导的模式不同。此外，异烟肼处理导致（还原型细胞色素P-450加CO）吸收峰最大值从450 nm移至451 nm。这种吸收峰的移动，再加上观察到微粒体细胞色素P-450的总含量未升高，表明有一种细胞色素P-450的产量增加。异烟肼处理后恩氟烷脱氟的极大增强特别令人感兴趣，因为尚未发现包括苯巴比妥、3-甲基胆蒽、苯妥英和β-萘黄酮在内的其他酶诱导剂能将恩氟烷脱氟提高到具有临床意义的水平。
