Extrahepatic tissue distribution, covalent binding, and toxicity of halothane in control and phenobarbital-pretreated...

Single anesthetic (11.5 mmole/kg) and nonanesthetic (4.6 mmole/kg) doses of 1-14C-halothane were administered separately to control and phenobarbital-pretreated rats by the intraperitoneal route. Tissue distribution and covalent binding of the anesthetic agent in the liver, lung, and kidney were determined at 4 and 24 hours after administration. Histopathological examination of the tissues revealed that halothane produced necrosis only in the livers of phenobarbital-pretreated rats and only after a period of 24 hours following the anesthetic dose. The lung and kidney appeared normal in all test animals. The liver was the major organ for the uptake, metabolism, and covalent binding of halothane metabolites to tissue proteins. Although similar metabolic activity was observed in the kidney and lung, toxic levels of the halothane metabolites were apparently not attained in these extrahepatic tissues in either control or phenobarbital-pretreated rats.