Munson E S, Malagodi M H, Shields R P, Tham M K, Fiserova-Bergerova V, Holaday D A, Perry J C, Embro W J
Clin Pharmacol Ther. 1975 Dec;18(6):687-99. doi: 10.1002/cpt1975186687.
Because of reports of fluroxene toxicity in man, the effect of phenobarbital treatment on the toxicity and metabolism of fluroxene was studied in 9 rhesus monkeys. Six monkeys that were exposed to a mean calculated alveolar fluroxene concentration of 5.8% for 4-hr periods up to a total of 16 hr showed no evidence of toxicity. Two animals were sacrificed after a single 4-hr exposure to obtain control measures of fluroxene metabolites in tissues. Four monkeys that had previously survived received exposures to fluroxene and 3 monkeys that had no exposure to fluroxene died during fluroxene anesthesia after treatment with phenobarbital (mean time, 3 hr). Toxicity was manifested by arterial hypotension, pulmonary edema, and arterial hypoxemia. Phenobarbital treatment enhanced production of fluroxene metabolites, including the highly toxic trifluoroethanol. Concentrations of trifluoroethanol in mixed-expired gas, blood, and urine, and of total nonvolatile fluorine in blood, urine, and tissues of animals treated with phenobarbital were 2 to 10 times as in control animals. The results suggest that the rhesus monkey is a valuable model for the study of fluroxene pharmacology and that inclusion of an enzyme-inducing challenge in the evaluation of potential toxicity of other anesthetics seems warranted.
由于有人类氟烯中毒的报道，因此在9只恒河猴身上研究了苯巴比妥治疗对氟烯毒性和代谢的影响。6只猴子暴露于平均计算肺泡氟烯浓度为5.8%的环境中，每次4小时，总共暴露16小时，未显示出毒性迹象。2只动物在单次暴露4小时后被处死，以获取组织中氟烯代谢物的对照测量值。4只先前存活的猴子接受了氟烯暴露，3只未接触过氟烯的猴子在苯巴比妥治疗后的氟烯麻醉期间死亡（平均时间为3小时）。毒性表现为动脉低血压、肺水肿和动脉低氧血症。苯巴比妥治疗增强了氟烯代谢物的产生，包括高毒性的三氟乙醇。接受苯巴比妥治疗的动物的混合呼出气体、血液和尿液中的三氟乙醇浓度，以及血液、尿液和组织中的总非挥发性氟浓度是对照动物的2至10倍。结果表明，恒河猴是研究氟烯药理学的有价值模型，并且在评估其他麻醉剂的潜在毒性时纳入酶诱导激发似乎是有必要的。
