Abstract
Metabolism study of N-(1-methyl-1-phenylethyl)-2-bromo-3, 3-dimethylbutanamide (bromobutide) in mice was carried out as single oral administration (5mg/kg) of 14C-carbonyl labeled bromobutide, and the results were compared with those of rats. Dosed 14C was rapidly excreted into urine (major) and feces (minor) in mice, while in rats dosed 14C was mainly excreted into feces. Levels of 14C-residues in tissues examined in mice were less than 0.1μg bromobutide equivalents per gram tissue and lower than those in rats on the 7th day after administration. The major biotransformations of bromobutide at the initial stage were aromatic hydroxylation in mice and ω-hydroxylation of t-butyl group and aromatic hydroxylation in rats. A glucuronide of p-hydroxylated product of bromobutide, was formed as a common and major product in liver of both species, but was excreted into blood and urine in mice and into bile in rats. These differences in species were presumably derived from different molecular selectivities in mice and rats for biliary secretion of the glucuronide. Judging from the higher quantity of polar metabolites in rats, compounds in bile were subjected to further biotransformation, e. g. debromination in the course of enterohepatic circulation observed. The major bioreaction of bromobutide at the initial stage was suggested to be oxidation, however, ca. 12.4% of bromobutide was estimated to be converted to oxidation products after debromination.
