EFFECTS OF CIMETIDINE AND RANITIDINE ON HALOTHANE METABOLISM AND HEPATOTOXICITY IN AN ANIMAL-MODEL

  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (1) , 106-110
Abstract
The effects of two H2-receptor antagonists, cimetidine and ranitidine, on halothane metabolism and hepatotoxicity in the hypoxic Fisher 344 rat model for halothane hepatitis were determined. In this model, liver injury is caused by toxic intermediates formed during metabolism of halothane by a reductive pathway. Administration of cimetidine (120 mg/kg i.p.) 20 min prior to anethesia led to inhibition of the reductive pathway, as assessed by measurement of the exhaled metabolites, 2-chloro-1,1,1-trifluoroethane and 2-chloro-1,1-difluoroethylene, during anesthesia, and urinary F- excretion in the 22-h postanesthesia period. Oxidative metabolism of halothane, assessed by serum Br- concentrations 22 h postanesthesia, was unaffected. Cimetidine administration provided partial protection against the hepatotoxic effect of halothane, as indicated by serum alanine aminotransferase activities 22 h postanesthesia. When ranitidine hydrochloride (120 mg/kg i.p.) was administered prior to anesthesia, reductive metabolism of halothane was unaffected, but the oxidative pathway was slightly inhibited. Ranitidine did not provide protection against halothane-induced liver injury. Halothane hepatotoxicity in the hypoxic rat is evidently due to toxic intermediates formed during the reductive metabolism of halothane.

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