Rice S A, Sbordone L, Mazze R I
Anesthesiology. 1980 Dec;53(6):489-93. doi: 10.1097/00000542-198012000-00009.
The possibility that enflurane defluorination is increased following treatment with isoniazid was investigated in male Fischer 344 rats. The effects of various isoniazid dosage regimens on the hepatic microsomal defluorination rates of enflurane were compared with those of several other ether anesthetics, and the conditions for production of maximal enflurane defluorination rates were determined. Seven to ten days of treatment with 50 mg/kg/day isoniazid (Nydrazid) resulted in maximal rates of defluorination of methoxyflurane, enflurane, isoflurane, and sevoflurane with no overt sign of toxicity. Compared with saline treatment of control rats, isoniazid increased defluorination of enflurane 370 per cent, methoxyflurane 259 per cent, sevoflurane 283 per cent, and isoflurane 168 per cent. Previous studies have shown that while the enzyme inducer phenobarbital increased in vitro rates of methoxyflurane defluorination approximately 1000 per cent, the rate of enflurane defluorination remained unchanged or increased by 100 per cent at most. In this study, enhanced hepatic microsomal defluorination was not associated with an increase in cytochrome P-450 per mg protein. Anesthetic defluorination rates were not altered by treatment with chlorobutanol, the preservative contained in Nydrazid.
在雄性Fischer 344大鼠中研究了异烟肼治疗后恩氟烷脱氟增加的可能性。将异烟肼不同给药方案对恩氟烷肝微粒体脱氟率的影响与其他几种醚类麻醉剂的影响进行了比较，并确定了产生最大恩氟烷脱氟率的条件。用50mg/kg/天的异烟肼（尼肼）治疗7至10天，可使甲氧氟烷、恩氟烷、异氟烷和七氟烷的脱氟率达到最大值，且无明显毒性迹象。与对照大鼠的盐水治疗相比，异烟肼使恩氟烷脱氟增加370%，甲氧氟烷增加259%，七氟烷增加283%，异氟烷增加168%。先前的研究表明，虽然酶诱导剂苯巴比妥使甲氧氟烷的体外脱氟率增加约1000%，但恩氟烷的脱氟率保持不变或最多增加100%。在本研究中，肝微粒体脱氟增强与每毫克蛋白质中细胞色素P - 450的增加无关。尼肼中含有的防腐剂氯丁醇处理不会改变麻醉剂的脱氟率。
