Metabolism and Excretion of [14C] Febuxostat, a Novel Nonpurine Selective Inhibitor of Xanthine Oxidase, in Healthy Male Subjects

Absorption, metabolism, and excretion of one 80 mg oral dose of [14C] febuxostat ([thiazole‐4‐14C] 2‐[3‐cyano‐4‐isobutoxyphenyl]‐4‐methyl‐5‐thiazolecarboxylic acid) were studied in 6 healthy subjects. Mean cumulative recovery in excreta was 94% (49% urine and 45% feces) of the dose over 9 days; 87% of the dose was profiled. Seventeen radioactive peaks were observed in urine and fecal chromatograms. Unchanged febuxostat contributed to a combined total in excreta of 10% to 18% of the dose, indicating that it was extensively metabolized and well absorbed. Metabolites were 67M‐1 (10%) and 67M‐2 (11%) hydroxylated febuxostat, febuxostat acyl‐glucuronide (30%), 67M‐4 di‐carboxylic acid (14%), 67M‐1 sulfate conjugate (3%), and dehydrated 67M‐1/67M‐2 acyl‐glucuronide (0.5%). Febuxostat and these metabolites accounted for 82% of profiled dose; unidentified peaks individually contributed