Results in rats suggest that scission of the C-H bond is not a determining factor in the hepatotoxicity of halothane, since no apparent differences in liver injury were observed between halothane and d-halothane. Also, no significant changes between halothane and d-halothane were found in the levels of those metabolites produced during the reductive biotransformation of halothane (F- and the volatile metabolites, CDE and CTE). However, deuterium substitution markedly reduced the oxidative biotransformation of halothane, as evidenced by the 60% decrease in debromination. The covalent binding data also indicate that scission of the C-H bond does not occur during reductive bioactivation of halothane, since the 3H was retained under reductive conditions. The differences in stoichiometry of the binding of 3H-halothane and 14C-halothane are interesting and may indicate that different reactive intermediates exist for binding to lipid or protein and/or for O2 or N2 atmospheres, or reflect isotope effects or isotope exchange reactions. However, binding of 3H-halothane equivalents may be a useful marker for reductive biotransformation of halothane and its associated toxicity.
|Original language||English (US)|
|Issue number||3 SUPPL|
|State||Published - Jan 1 1979|
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine