Differential effects of chronic ethanol feeding on cytochrome P-448- and P-450-mediated drug metabolism in the rat

Mack C. Mltchell, Anastacio Hoyumpa, Steven Schenker, Rashmi V. Patwardhan

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The effects of chronic ethanol feeding on cytochrome P-448- and P-450-mediated drug metabolism have been studied both in vivo and in vitro in the rat, using caffeine, phenacetin, antipyrine and aminopyrine as test substrates. N-Demethylation of aminopyrine (P-450 mediated) was increased both in vivo and in vitro in rats after chronic ethanol feeding (P < 0.05) whereas in vivo N-demethylation of caffeine and O-dealkylation of phenacetin (P-448 mediated) were unchanged in the same animals. N-rmDemethylation of antipyrine was increased by both phenobarbital and 3-methylcholanthrene pretreatment and by chronic ethanol feeding (P < 0.05), possibly due to cytochrome P-450 induction. Furthermore, the Michaelis affinity constants. Km, for hepatic microsomal aminopyrine N-demethylase and antipyrine N-demethylase were lower in chronic ethanol-fed animals (P < 0.05), suggesting a qualitative change in the enzymes resulting in greater substrate affinity. These findings suggest a differential effect of chronic ethanol feeding on the induction of cytochrome P-450- and cytochrome P-448-mediated drug metabolism, with a greater effect on the former microsomal system.

Original languageEnglish (US)
Pages (from-to)695-699
Number of pages5
JournalBiochemical Pharmacology
Volume31
Issue number5
DOIs
StatePublished - Mar 1 1982

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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