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Fluroxene toxicity induced by phenobarbital
Author(s) -
Munson Edwin S.,
Malagodi Marjorie H.,
Shields Robert P.,
Tham Min K.,
FiserovaBergerova Vera,
Holaday Duncan A.,
Perry Joel C.,
Embro William J.
Publication year - 1975
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1975186687
Subject(s) - phenobarbital , toxicity , medicine , pharmacology , urine
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 high 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.