Factors affecting the formation of chlorotrifluoroethane and chlorodifluoroethylene from halothane

R. M. Maiorino, I. G. Sipes, A Jay Gandolfi, B. R. Brown, R. C. Lind

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Since CF 3CH 2Cl and CF 2CHCl are probably the products of reactive intermediates formed during the reductive metabolism of halothane (CF 3CHClBr), factors affecting their in vitro and in vivo formation were investigated. In vitro studies with rat hepatic microsomes showed that CF 3CH 2Cl and CF 2CHCl are produced by cytochrome P-450 mediated reductive pathways which were inhibited by the presence of CO. Under conditions of exposure known to promote halothane hepatotoxicity in phenobarbital treated rats (1% halothane, 14% oxygen), the hepatic and blood concentrations of the volatile metabolites were enhanced. Central venous levels of the volatile metabolites were much higher than the concentration in peripheral vessels. The CF 3CH 2Cl/CF 2CHCl ratio in blood was approximately three, whereas the ratio in vitro was almost unity. Liver levels of the two volatile metabolites greatly exceeded the blood levels, but interestingly they were present in equivalent concentrations. The differences in the ratio of CF 3CH 2Cl to CF 2CHCl may be explained by the fact that CF 2CHCl is further degraded under oxidative conditions, whereas CF 3CH 2Cl appears relatively stable. Measurement of these metabolic products in patients undergoing halothane anesthesia may permit rapid detection of an unusually high level of halothane biotransformation along its hepatotoxic pathway.

Original languageEnglish (US)
Pages (from-to)383-389
Number of pages7
JournalAnesthesiology
Volume54
Issue number5
StatePublished - 1981

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Halothane
Liver
Carbon Monoxide
Phenobarbital
Biotransformation
Microsomes
Cytochrome P-450 Enzyme System
Anesthesia
Oxygen
In Vitro Techniques

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Maiorino, R. M., Sipes, I. G., Gandolfi, A. J., Brown, B. R., & Lind, R. C. (1981). Factors affecting the formation of chlorotrifluoroethane and chlorodifluoroethylene from halothane. Anesthesiology, 54(5), 383-389.

Factors affecting the formation of chlorotrifluoroethane and chlorodifluoroethylene from halothane. / Maiorino, R. M.; Sipes, I. G.; Gandolfi, A Jay; Brown, B. R.; Lind, R. C.

In: Anesthesiology, Vol. 54, No. 5, 1981, p. 383-389.

Research output: Contribution to journalArticle

Maiorino, RM, Sipes, IG, Gandolfi, AJ, Brown, BR & Lind, RC 1981, 'Factors affecting the formation of chlorotrifluoroethane and chlorodifluoroethylene from halothane', Anesthesiology, vol. 54, no. 5, pp. 383-389.
Maiorino, R. M. ; Sipes, I. G. ; Gandolfi, A Jay ; Brown, B. R. ; Lind, R. C. / Factors affecting the formation of chlorotrifluoroethane and chlorodifluoroethylene from halothane. In: Anesthesiology. 1981 ; Vol. 54, No. 5. pp. 383-389.
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