Biotransformation of BOF-4272, a sulfoxide-containing drug, in the cynomolgus monkey.

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 pharmacokinetics and detailed metabolic pathways of BOF-4272 in the cynomolgus monkey, which were investigated using the metabolites found in plasma, urine, and faeces after intravenous and oral administration. M-4 was the main metabolite in plasma after intravenous administration. M-3 and M-4 were the main metabolites in plasma after oral administration. The Cmax and AUC(0-t) of M-4 were the highest of all the metabolites after intravenous administration. The Cmax and AUC(0-t) of M-3 were the highest of all the metabolites, and those of M-4 were the second highest, after oral administration. M-4 and M-3 were the main metabolites detected in urine and faeces, respectively, after intravenous administration, with M-4 and M-3 at 47.2% in urine and 19.1% in faeces, respectively, within 120 h after administration. M-4 was the only metabolite detected in urine after oral administration, at about 5% within 120 h after administration. M-3 was detected in faeces at 17.0% within 120 h after oral administration. These results suggest that, in the cynomolgus monkey, BOF-4272 is rapidly biotransformed to a main metabolite (M-4, a sulphoxide-containing metabolite of BOF-4272) and that M-4 is mainly excreted in urine and possibly also in bile, with subsequent conversion to M-3 by the intestinal flora. It is expected that the biotransformation of BOF-4272 would be similar in healthy human volunteers.