Accumulation in Murine Amniotic Fluid of Halothane and its Metabolites

Publisher Website
Google Scholar
Abstract
The distribution of radioactivity in pregnant mice was registered at 0, 1, 4 and 24 h after a 10 min period of inhalation of 14C-halothane. Autoradiographic methods were used to distinguish between the distribution of volatile (nonmetabolized) halothane, water-soluble metabolites and firmly tissue-bound metabolites. While volatile radioactivity was seen predominantly at short survival intervals, e.g., in body fat, blood, brain and liver, metabolites accumulated with time. Peak values occurred at 4 h in most organs (measured with liquid scintillation as well). The most remarkable findings were the high concentrations of radioactivity in amniotic fluid (and the ocular fluids of adults) with peak values at 4 h and high concentrations still prevailing at 24 h after inhalation. This activity probably represented only partly volatile halothane and mostly nonvolatile metabolites. High activity of metabolites was seen in the neuroepithelium of the embryo in early gestation. Firmly tissue-bound metabolites, still remaining after washing the tissues with trichloroacetic acid and organic solvents, were found in the nasal mucosa, trachea and bronchial tree and in (presumably centrilobular) zones of the liver of adults after inhalation and 5 day old mice after i.p. injection, indicating the formation of reactive metabolites in these organs. Firmly tissue-bound activity was not observed in the corresponding fetal organs.