Abstract
The effect of aging on the inhibition by ethanol of drug metabolism activity was examined in liver microsomes of female Fischer 344 rats aged 4, 14 and 24 months. Inhibition of aniline hydroxylase activity in microsomes from 4-month-old females occurred at low concentrations of ethanol (0.1 mM) and was predominentaly competitive. Aging was associated with a significat increase in apparent Km for aniline in the absence of ethanol (24 ± 2, 20 ± 2 and 32 ± 1μM in microsomes from 4-, 14- and 24-month-old rats, respectively) and a change from competitive to non-competitive inhibition by ethanol. Inhbition of benphetamine N-demethylase activity occurred only at high concentrations of ethanol (100 mM) and was non-competitive in nature. There was no significant effects of aging on the kinetics of the reaction or the type of inhibition produced by ethanol. Microsomal ethanol oxidation rates were measured in liver microsomes of 4-, 15- and 25-month-old Fischer 344 rats of both sexes. Ethanol oxidation in males was greater than in females and was decreased significantly in old age. Ethanol oxidation in female rats was unaffected by aging. The results suggest that significant changes in drug/ethanol interactions can occur as a consequence of aging.
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