Bioactivation and covalent binding of halothane in vitro: Studies with [3H]- and [14C]halothane

A. J. Gandolfi, R. D. White, I. G. Sipes, L. R. Pohl

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62 Scopus citations


To determine if the hydrogen atom of halothane (CF3CHBrCl) is retained on the reactive intermediates that covalently bind to microsomal lipids and protein [3H]halothane and [14C]halothane were incubated with rat hepatic microsomes and a NADPH generating system. Both [3H]- and [14C]halothane were bioactivated and bound to a greater degree when incubations were performed in a N2 atmosphere rather than an O2 atmosphere. In fact, covalent binding of 3H-equivalents did not occur under an O2 atmosphere. Binding of [3H]- and [14C] halothane equivalents was significantly enhanced when hepatic microsomes from phenobarbital- or Aroclor 1254-treated rats were used in the incubations. Omission of NADPH or incubation with CO was inhibitory to the binding of both [3H]- and [14C]halothane. The apparent kinetic constants for binding of halothane equivalents, Km and Vmax indicate a significantly higher Km but lower Vmax for the formation and/or binding of 3H-binding equivalents. The results indicate that halothane is primarily bioactivated under conditions that promote its reductive metabolism and that this reductive metabolism does not involve cleavage of the carbon-hydrogen bond of halothane. Differences in binding under N2 and O2 as well as between [3H]- and [14C]halothane suggest that multiple reactive intermediates may form during the biotransformation of halothane.

Original languageEnglish (US)
Pages (from-to)721-725
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
StatePublished - 1980

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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