BOF-4272, (+/-)-8-(3-methoxy-4- phenylsulfinylphenyl)pyrazolo[1,5-a]-1,3,5-
triazine-4(1H)-one, is a new
drug intended for the treatment of
hyperuricemia. This report describes the detailed metabolic pathways of
BOF-4272 in the dog. The metabolic pathways were investigated using the metabolites found in plasma, urine, and feces after intravenous or
oral administration of
BOF-4272, as well as the metabolites found in the liver S9 incubation mixture after the addition of
BOF-4272 or BOF-4269. BOF-4269 (the
sulfide metabolite of
BOF-4272) was the only metabolite detected in plasma and feces after the intravenous or
oral administration of
BOF-4272. BOF-4269 was detected in dog plasma after a lag time following the
oral administration of
BOF-4272, and the Cmax and AUC0-t of BOF-4269 were higher in fed dogs than in fasted dogs after the
oral administration of
BOF-4272. A small amount of BOF-4269 was detected in dog plasma immediately after the
intravenous administration of
BOF-4272. Only BOF-4276 (the
sulfone metabolite of
BOF-4272) was detected in the S9 incubation mixture after the addition of
BOF-4272. Mainly
BOF-4272 was detected and small amounts of BOF-4276 and M-1 (the hydroxy metabolite of BOF-4269) were detected in the S9 incubation mixture after the addition of BOF-4269. These findings suggest that
BOF-4272 is mainly metabolized to BOF-4269 by the intestinal flora in dogs, whereas little of this
drug is metabolized to BOF-4269 in the dog liver. In conclusion, this work has allowed us to formulate the proposed metabolic pathways of
BOF-4272 in the dog.