Effects of ethanol on microsomal drug metabolism in aging female rats. II. Inhibition.
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 predominantly competitive. Aging was associated with a significant increase in apparent Km for aniline in the absence of ethanol (24 +/- 2, 20 +/- 2 and 32 +/- 1 microM in microsomes from 4-, 14- and 24-month-old rats, respectively) and a change from competitive to non-competitive inhibition by ethanol. Inhibition of benzphetamine N-demethylase activity occurred only at high concentrations of ethanol (100 mM) and was non-competitive in nature. There were 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.
Rikans
L E
LE
Department of Pharmacology, University of Oklahoma College of Medicine, Oklahoma City 73190.
D000375:Aging / Q000378:metabolism*; D000815:Aniline Hydroxylase / Q000378:metabolism*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D000431:Ethanol; D000815:Aniline Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases