Inhibitory effect of isoflurane upon oxidative metabolism of halothane.

The effect of isoflurane upon halothane metabolism was studied in rats exposed to mixtures of subanesthetic concentrations of isoflurane (0.015-0.32%) and halothane (0.062%). The extent of halothane metabolism was determined from concentrations of halothane and its metabolites (total nonvolatile fluorine, 1,1,1-trifluoro-2-chloroethane and 1,1-difluoro-2-chloroethylene) in tissues of rats. At the end of exposures lasting 3 hr, distribution of halothane in tissues indicated that the bioavailability of halothane in liver was unaffected by exposure to isoflurane. Isoflurane, however, significantly inhibited the oxidative metabolism of halothane, as indicated by reduced concentrations of total nonvolatile fluorine in tissues. The inhibition is concentration-dependent. Isoflurane enhances the reductive metabolism of halothane, as indicated by increased concentrations of volatile metabolites in liver. Exposure to nitrous oxide (2.2-50%) had no effect on halothane metabolism. The mechanism of the inhibitory effect remains to be explained.