Differential effects of chronic ethanol feeding on cytochrome P-448- and P-450-mediated drug metabolism in the rat |
| |
Authors: | Mack C. Mltchell Anastacio Hoyumpa Steven Schenker Rashmi V. Patwardhan |
| |
Affiliation: | Vanderbilt University School of Medicine, and Veterans Administration Medical Center, Nashville, TN 37203, U.S.A. |
| |
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 vivoN-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. |
| |
Keywords: | Address correspondence to: Mack C. Mitchell M.D. VA Medical Center Rm B-230 1310 24th Avenue South Nashville TN 37203 U.S.A.. |
本文献已被 ScienceDirect 等数据库收录! |
|