Drug biotransformation in microsomes from the fetal stumptailed macaque, Macaca arctoides: hepatic N-demethylation

Abstract

The kinetics of the N-demethylation of benzphetamine, ethylmorphine, meperidine, and methadone have been studied in microsomes isolated from livers of the fetal stumptailed macaque (Macaca arctoides) during the last third of gestation. The apparent KM for each substrate did not change during this time period. Values were similar to those from livers of adult African green monkeys. The Vmax for each substrate, when expressed per mg of microsomal protein, did not change during the last third of gestation. N-demethylase activity (Vmax) per g of liver increased during the last third of gestation, as did the content of microsomal protein, cytochrome P-450 concentration, and liver weight. The amount of cytochrome P-450 per g of liver was greater in whole homogenates of the left physiological lobe than in those of the right physiological lobe of fetal liver obtained near term; no differences occurred in whole homogenates of the separate lobes of adult liver. This observation suggests that a differential capacity for drug (and possibly steroid) metabolism may exist between the two physiological lobes of fetal liver.