Species, sex, and developmental differences in the O- and N-dealkylation of ethylmorphine by hepatic microsomes.

3-O-[1'-14C]Ethylmorphine and ethylmorphine, respectively, were used to measure O- and N-dealkylase activities of hepatic microsomes. The well-known sex difference in the rate of N-delakylation in mature rats was not observed with O-dealkylation, nor did O-dealkylase activity increase as male rats reached maturity, as is the case with N-dealkylase activity. Accordingly, O-dealkylation represents only about 20% of the total dealkylase activity (O- + N-) in mature male rats, but about 50% in mature female rats. A comparison of the O- and N-dealkylating activities of hepatic microsomes from rats, mice, guinea pigs, and rabbits showed that both the rates of O- and N-dealkylation and the ratio of the two reactions vary greatly among animal species. These studies contribute to the evidence that different cytochrome P-450-dependent mono-oxygenase systems are involved in the O- and N-dealkylation of opium alkaloids.