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.