RT Journal Article SR Electronic T1 SEX-DEPENDENT DIFFERENCES IN DRUG METABOLISM IN THE RAT JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 285 OP 292 VO 2 IS 3 A1 G. M. COHEN A1 G. J. MANNERING YR 1974 UL http://dmd.aspetjournals.org/content/2/3/285.abstract AB Microsomal ethylmorphine N-demethylase activity increased with age in male rats, but decreased with age in female rats. Relative to the cytochrome P-450 content of microsomes, there was no temporal change or sex difference in the magnitudes of the ethylmorphine binding spectrum (type I) and NADPH-cytochrome P-450 reductase activities. Thus, neither of these parameters correlated with observed temporal changes and sex differences in ethylmorphine N-demethylase activity. On the other hand, ethylmorphine-stimulated NADPH-cytochrome P-450 reductase activity was markedly greater in microsomes from males than from females, and the difference widened as the rats grew older. This was due entirely to an increase in activity in the microsomes from male rats. Differences in rates of ethylmorphine N-demethylation correlated well with differences in Δ reductase activity (reductase activity in the presence of ethylmorphine minus reductase activity in the absence of ethylmorphine). A 1 : 1 relationship was observed between Δ reductase activity and the rate of ethylmorphine N-demethylation. NADH synergism of NADPH-dependent ethylmorphine N-demethylation changed little with age but was greater in microsomes from male than from female rats. Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics