苯妥英（DPH）治疗对大鼠甲氧氟烷代谢的影响。

Effect of phenytoin (DPH) treatment on methoxyflurane metabolism in rats.

作者信息

Caughey G H, Rice S A, Kosek J C, Mazze R I

出版信息

J Pharmacol Exp Ther. 1979 Aug;210(2):180-5.

Abstract

The toxicity and metabolism of the fluorinated anesthetic methoxyflurane were compared in Fischer 344 rats pretreated with phenytoin or phenobarbital. Treatment with either drug potentiated the polyuric effects of methoxyflurane by more than 100%. Also, serum inorganic fluoride (F-) levels and urinary F- excretions after methoxyflurane exposure were comparable in phenytoin- and phenobarbital-treated rats, a 26 to 49% increase as compared to rats treated with methoxyflurane alone. In vitro, 10-fold increases in the rate of hepatic microsomal methoxyflurane defluorination were observed after treatment of rats with either phenytoin or phenobarbital. Kinetic studies with microsomes demonstrated inhibition of methoxyflurane defluorination in the presence of phenytoin. Defluorination of three additional fluorinated ether anesthetics, enflurane, isoflurane and sevoflurane, also was examined in vitro. Phenytoin and phenobarbital treatment resulted in similar enhancement of defluorination of the latter two anesthetics, but not enflurane. Phenytoin and phenobarbital treatment increase defluorination of fluorinated ether anesthetics to approximately the same extent in vitro and in vivo in Fischer 344 rats.

摘要

在接受苯妥英或苯巴比妥预处理的Fischer 344大鼠中，对氟化麻醉剂甲氧氟烷的毒性和代谢进行了比较。用这两种药物中的任何一种进行治疗，均可使甲氧氟烷的多尿作用增强100%以上。此外，在接受苯妥英和苯巴比妥治疗的大鼠中，甲氧氟烷暴露后的血清无机氟（F-）水平和尿F-排泄量相当，与仅接受甲氧氟烷治疗的大鼠相比增加了26%至49%。在体外，用苯妥英或苯巴比妥治疗大鼠后，观察到肝微粒体甲氧氟烷脱氟速率增加了10倍。用微粒体进行的动力学研究表明，在苯妥英存在的情况下，甲氧氟烷脱氟受到抑制。还在体外研究了另外三种氟化醚麻醉剂恩氟烷、异氟烷和七氟烷的脱氟情况。苯妥英和苯巴比妥治疗使后两种麻醉剂的脱氟有类似增强，但对恩氟烷没有作用。在体外和体内，苯妥英和苯巴比妥治疗使Fischer 344大鼠中氟化醚麻醉剂脱氟增加的程度大致相同。