EFFECTS OF ALIPHATIC HALOGENATED HYDROCARBONS ON HEPATIC DRUG METABOLISM

Pretreatment of rats with CCl4 prolonged the sleeping times evoked by hexobarbital. The metabolism of hexobarbital by the isolated perfused rat liver was reduced after intoxication with CCl4 and may have been responsible, in part, for the enhanced action of the barbiturate. Poisoning with CCl4 impaired the oxidation of hexobarbital and aminopyrine as well as the reduction of p-nitrobenzoic acid by liver microsomes. The activity of the drug-metabolizing enzymes declined to about 10 per cent of normal within 8 hr and remained at low levels 24 hr after the administration of CCl4. The return of enzyme activity to normal levels started coincident with the disappearance of CCl4 from the liver and required about 8 days for completion. In contrast to the striking toxicity of carbon tetrachloride, drug metabolism was not reduced after the administration of methylene chloride, and chloroform evoked only a moderate impairment of aminopyrine demethylation. © 1968.