Comparison of the biotransformation and hepatotoxicity of halothane and deuterated halothane

I. G. Sipes, A Jay Gandolfi, L. R. Pohl, G. Krishna, B. R. Brown

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Abstract

To investigate the effect of deuterium substitution on the biotransformation and hepatotoxicity of halothane, male, phenobarbital-pretreated rats were exposed for 2 hr to 1% halothane or deuterated halothane (d-halothane) delivered in 14% O 2-85% N 2. The exposures were performed at mildly hypoxic conditions (14% O 2) since it was previously established that the decreased oxygen tension promotes both the reductive metabolism of halothane and halothane-induced liver injury. At the end of anesthesia or at 24 hr, the rats were sacrificed so that blood, liver and urine samples could be obtained for measurement of metabolites and assessment of liver damage. Deuterium substitution did not affect the levels of reductive metabolites of halothane (fluoride, CF 3CH 2Cl and CF 2CHCl nor did it alter the degree of hepatotoxicity as assessed by serum glutamic-pyruvic transaminase levels and morphological examination. The levels of oxidative metabolites (CF 3COOH and bromide) were significantly reduced at the end of anesthesia and at 24 hr. It is concluded that halothane-induced hepatotoxicity is initiated by reactive intermediates formed during its reductive metabolism and that cleavage of the C-H bond is not involved in this pathway. The oxidative biotransformation of halothane proceeds by an oxygen insertion reaction at the C-H bond. Thus, the increased stability of the C-D bond explains the reduction in oxidative metabolites observed after exposure to d-halothane.

Original languageEnglish (US)
Pages (from-to)716-720
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume214
Issue number3
StatePublished - 1980

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Halothane
Biotransformation
Deuterium
Liver
Anesthesia
Oxygen
Phenobarbital
Alanine Transaminase
Bromides
Fluorides
Urine
Wounds and Injuries

ASJC Scopus subject areas

  • Pharmacology

Cite this

Comparison of the biotransformation and hepatotoxicity of halothane and deuterated halothane. / Sipes, I. G.; Gandolfi, A Jay; Pohl, L. R.; Krishna, G.; Brown, B. R.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 214, No. 3, 1980, p. 716-720.

Research output: Contribution to journalArticle

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