Transient Inhibitory Effect of Isoflurane upon Oxidative Halothane Metabolism

The duration of inhibition of halothane oxidative metabolism by isoflurane was studied in rats exposed for 2 hr to an anesthetic concentration of isoflurane (0.6% inspired), followed by a 2-hr exposure to a subanesthetic concentration of halothane (0.06% inspired), starting either 0.5, 4, or 24 hr after the end of the isoflurane exposure. Other rats were exposed to halothane, isoflurane, or a mixture of both. Tissue levels of total nonvolatile fluorine were used as a measure of oxidative metabolism of halothane and hepatic levels of 1,1,1-trifluoro-2-chloroethane and 1,1-difluoro-2-chloroethylene as a measure of reductive metabolism of halothane. Isoflurane administered simultaneously with or 30 min prior to halothane significantly inhibited oxidative metabolism of halothane, but this inhibition was transient and was no longer apparent when halothane was administered 4 or 24 hr after the end of isoflurane anesthesia. The reductive metabolism of halothane was unaffected. This study suggests that isoflurane may transiently modify the action of some drugs administered during the perianesthesia period by inhibiting their oxidative metabolism. Differences in elimination kinetics of nonvolatile fluorine-containing metabolites after isoflurane and halothane exposure suggest the presence of an unidentified isoflurane metabolite.