Abstract
A previous study demonstrated that acute ethanol intoxication inhibits the rate of drug metabolism. To investigate the effects of chronic ethanol consumption on ethanol and drug metabolism, four alcoholic and four nonalcoholic volunteer subjects were given ethanol for one month under metabolic ward conditions. This resulted in accelerating the rate of disappearance of ethanol from the blood of the alcoholics and nonalcoholics from, respectively, 13.6 ± 2.4 and 13.8 ± 2.0 mg/100 ml/ hour during the control period to 18.5 ± 2.0 (P < 0.01) and 23.8 ± 2.0 (P < 0.05) after the ethanol period. In the same volunteer subjects, the rate of disappearance of meprobamate from the blood was also significantly accelerated from a mean half life of, respectively, 16.7 ± 2.5 and 13.7 ± 1.0 hours to 8.1 ± 1.5 (P < 0.02) and 8.2 ± 0.3 (P < 0.02). Urinary excretion of meprobamate was unaltered. Four to eight weeks after the end of the ethanol period the rate of disappearance of alcohol and meprobamate from the blood was restored to normal. The half life of pentobarbital was also measured in the four nonalcoholic subjects: there was a reduction from 35.1 ± 6.1 to 26.3 ± 6.3 hours after one month of ethanol feeding. To study the mechanism of these effects, rat littermates were pair-fed adequate diets with 36 per cent of calories either as ethanol or carbohydrates; the half life of meprobamate was 254 ± 36 minutes in control animals versus 138 ± 19 minutes in rats fed ethanol for twenty-eight days (P < 0.02). Liver slices and 9,000 g microsomal preparations obtained from rats fed ethanol for one to three months showed significant increases in rates of meprobamate metabolism. Our study therefore demonstrates that chronic ethanol ingestion results in accelerated drug clearance from the blood caused, at least in part, by enhanced hepatic microsomal drug metabolism. This (in addition to central nervous system adaptation) helps to explain the tolerance to ethanol and other drugs which is known to develop in alcoholics.
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