INHIBITION OF DRUG HYDROXYLATION IN VIVO BY ETHANOL ADMINISTRATION

In the rat, the pharmacokinetic behaviour of phenazone and aminophenazone (amidopyrine) is changed after administration of ethanol (3.2 ml/kg, p.o.). Urinary excretion studies show a biphasic effect on the elimination of certain metabolites formed by N-demethylation and C-hydroxylation. There is a significant decrease of elimination of these metabolites during the first 5-6 hours after the administration of ethanol. This is followed by a compensatory increase after the ethanol has been metabolized. In contrast, elimination of unchanged phenazone remains unaffected during the first 5 hours after ethanol administration, but is increased later. Correspondingly, the blood level of unchanged phenazone initially shows no difference compared to control but decreases more slowly after ethanol administration. The blood level of the main metabolites of aminophenazone, determined as total aminoantipyrine, is diminished after ethanol and shows considerable delay in reaching its maximum. The observed changes in the pharmacokinetic behaviour of the drugs tested are due to reversible inhibition of microsomal N-demethylation and C-hydroxylation in the liver by ethanol. Such inhibition of microsomal drug metabolism by ethanol may alter the duration and intensity of action of certain drugs when they are given in combination with ethanol. © 1969 Springer-Verlag.