The Combined Effect of Ethanol and Phenobarbital on the Activities of Hepatic Drug Metabolizing Enzymes in Rats

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Abstract
The effect of feeding ethanol (15 % v/v) and/or phenobarbital (0.05 % w/v) in drinking water on the rate of metabolism of methylaniline and p‐nitrobenzoic acid, and on the microsomal protein and cytochrome P‐450 contents in rat liver was studied. Animals treated with ethanol for 3 days showed an increase in N‐demethylation of methylaniline of 88 %, whereas the nitroreduction of p‐nitrobenzoic acid was inhibited by 47 %. Ethanol and phenobarbital had a synergistic action on N‐demethylation. Ethanol inhibited the induction of nitroreduction by phenobarbital. Ethanol, like phenobarbital, increased microsomal protein and they acted synergistically in this respect. Ethanol, like phenobarbital, caused a significantly greater increase in rnicrosomal cytochrome P‐450 than in microsomal protein content, and they also acted synergistically on cytochrome P‐450.