Metabolism of N-(1-Methyl-1-phenylethyl)-2-bromo-3, 3-dimethylbutanamide (Bromobutide) in Rats

Abstract

With single oral administration of ¹⁴C-carbonyl- or ¹⁴C-phenyl-labeled bromobutide, N-(1-methyl-1-phenylethyl)-2-bromo-3, 3-dimethylbutanamide to male and female rats at the rate of 5mg/kg b. w., the radiocarbon was excreted rapidly and completely into the feces and urine. Residue levels of ¹⁴C in tissues and organs were less than 0.11μg bromobutide eq/g tissue in male and 0.07μg bromobutide eq/g tissue in female on the 7th day after administration. The bromobutide dosed was mainly metabolized by phenyl- and t-butyloxidation, debromination, and glucuronidation. In particular, the metabolites which had received the oxidation reactions accounted for 32-40% and 58-63% of the bromobutide dosed, respectively and the debrominated products including debromo-bromobutide amounted to more than 50% forming the major metabolic pathways. In contrast, the hydroxylated products of the methyl group in amine moiety were found only in small quantity and little amide hydrolysates, sulfate- and amino acid-conjugates were detected in feces and urine. When male rats were treated with higher dose (125mg/kg b. w.) of ¹⁴C-carbonyl-bromobutide, the less oxidized metabolites were excreted to higher extents, but little changes were observed in the members of metabolites.