Febarbamate: metabolism in the rat

The metabolism of 1-(3-butoxy-2-carbamoyloxypropyl)-5-ethyl-5-phenyl-(1H,3H,5H)-pyrimidine-2,4,6- trione (febarbamate) in the rat has been studied after oral administration. Using high performance liquid chromatography, fifteen metabolites were isolated from urine, purified and identified by MS and NMR spectrometry. Febarbamate was extensively metabolized and only traces of the unchanged compound were found. The oxygen dealkylation and the (omega-1)-hydroxylation of n-butyl chain are the predominant pathways of the biotransformation and lead to the formation of two major metabolites: 1-(2-carbamoyloxy-3-hydroxypropyl)-5-ethyl-5-phenyl-(1H,3H,5H)-pyrimidine-2,4,6,-trione and 1-[3-(3-hydroxybutoxy)-2-carbamoyloxypropyl]-5-ethyl-5-phenyl-(1H,3H,5H)-pyrimidine-2,4,6,-trione. Hydrolytic cleavage of the ester function, the pyrimidine ring opening and p-hydroxylation of phenyl ring play a less important role. The stepwise degradation of n-butyl chain was also observed.