THE EFFECT OF STARVATION ON THE KINETICS OF DRUG OXIDATION BY HEPATIC MICROSOMAL ENZYMES FROM MALE AND FEMALE RATS

¹ Laboratories of Chemical Pharmacology, National Heart and Lung Institute and National Cancer Institute, National Institutes of Health, Bethesda, Maryland

The effect of 72-hour starvation on the kinetics of drug oxidation in hepatic microsomes was studied in male and female rats. In both sexes, starvation markedly decreased the yield of microsomal protein per whole liver. In male rats, starvation elicited significant increases in cytochrome P-450 content, in apparent K_m and V_max for the N-demethylation of ethylmorphine and in V_max for the hydroxylation of aniline. In female rats, starvation had no significant effect upon any of these parameters except for an increase in V_max for aniline hydroxylation. A sex difference was also observed with regard to the effect of starvation followed by 72-hour refeeding. Despite the significant changes in the kinetics of ethylmorphine demethylation produced by starvation in male rats, there were no accompanying changes in spectral properties (K_s, A_max) of the microsomes. Starvation of male rats also elicited marked reduction in the apparent K_m and V_max for the oxidation of hexobarbital and an increase in K_m for aminopyrine demethylation without affecting V_max for the latter substrate. The duration of hexobarbital-induced hypnosis was prolonged in starved male rats. The data indicate that the effect of starvation on the kinetics of drug oxidation by rat liver microsomes varies markedly with the sex of the rats and the particular substrate investigated.