Perdeuteration of methoxyflurane reduces production of fluorometabolites in mice.
The fluorometabolites of perdeuterated methoxyflurane (D-MOF) compared to the nondeuterated form (H-MOF) were studied in mice. Inorganic fluoride (F) and an organic acid labile fluorometabolite (OALF) were determined at various post-administration times. At 100 minutes after D-MOF, F was decreased 32-38% and OALF was down to 33-45%. After 300 minutes F was 56% less and OALF was 46% less after D-MOF administration. OALF increased 35-38% when H-MOF and D-MOF were diluted in oil compared to the undiluted forms. At three times (10, 30, and 100 minutes) D-MOF resulted in reductions of F to 31-38% of values produced by H-MOF. Also, OALF was reduced to 38-46% with D-MOF compared to H-MOF. These studies suggest that the use of D-MOF in mice results in a significant decrease in the appearance of the fluorometabolites F and OALF. The accumulation of metabolites is thought to be responsible for nephrotoxicity of MOF; therefore, D-MOF should be a much safer agent for use in general anesthesia.
Department of Oral Biology, School of Dentistry, Medical College of Georgia, Augusta 30912.
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Fry
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Ciarlone
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005459:Fluorides / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008733:Methoxyflurane / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D012018:Reflex / Q000187:drug effects
D008733:Methoxyflurane; D005459:Fluorides