Factors Affecting the Formation of Chlorotrifluoroethane and Chlorodifluoroethylene from Halothane

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Abstract
Since CF3CH2Cl and CF2CHCl are probably the products of reactive intermediates formed during the reductive metabolism of halothane (CF3CHClBr), factors affecting their in vitro and in vivo formation were investigated. In vitro studies with rat hepatic microsomes showed that CF3CH2Cl and CF2CHCl 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% O2), the hepatic and blood concentrations of the volatile metabolites were enhanced. Central venous levels of the volatile metabolites were higher than the concentration in peripheral vessels. The CF3CH2Cl/CF2CHCl ratio in blood was .apprx. 3 but the ratio in vitro was almost unity. Liver levels of the 2 metabolites exceeded the blood levels, but they were present in equivalent concentrations. The differences in the ratio of CF3CH2Cl to CF2CHCl may be explained by the fact that CF2CHCl is further degraded under oxidative conditions but CF3CH2Cl appears relatively stable. Measurement of these metabolic products in patients undergoing anesthesia may permit rapid detection of an unusually high level of halothane biotransformation along its hepatotoxic pathway.