The effects of deuteration on the metabolism of halogenated anesthetics in the rat

Abstract

The authors studied the effects of substituting deuterium for hydrogen in several volatile anesthetics on their metabolism in the Fischer rat. Substitution of deuterium in the ethyl portion of methoxyflurane increased the metabolic production of fluoride ion by 9 percent when administered at a concentration of 0.05 percent. Total replacement of hydrogen by deuterium resulted in a 29 percent decrease in the amount of fluoride produced, while deuteration of only the methoxyl group produced a 33 percent decrease in fluoride produced. Deuteration of halothane resulted in a 15 or 26 percent decrease in serum bromide at 0.75 percent or 1.0 percent, respectively. Deuteration in the ethyl portions of enflurane and two experimental agents, CF2HOCF2 CFBrH and CF2HOCF2CCl2H resulted in 65, 76, and 29 percent decreases in urinary fluorise, respectively. Anesthesia with deuterated chloroform at a concentration of 0.36 percent produced a 35 percent decrease in serum glutamic pyruvic transaminase (SGPT). It is concluded that deuteration of volatile anesthetics changes their metabolism, in most cases producing decreases in metabolism. This effect may lessen the organ toxicity believed to occur with some of these anesthetics.