Excretion of phenazopyridine and its metabolites in the urine of humans, rats, mice, and guinea pigs.

The metabolism of the urinary tract analgesic phenazopyridine [2,6-diamino-3-(phenylazo)pyridine; PAP] was studied in the urine of humans, rats, mice, and guinea pigs. Urinary excretion was rapid in human and guinea pig, but in the rat and mouse it was slower and there was significant fecal excretion. Metabolism of PAP was extensive in all four species, and there were marked quantitative differences in the routes of metabolism. The extent of azo bond cleavage was high in the mouse and guinea pig, moderate in the rat, and low in humans. Hydroxylation of both the phenyl and pyridyl rings of PAP was observed in all species. In the human, 5-hydroxyl PAP was the major metabolite (48.3% of the dose). It was concluded that there are marked species differences in the metabolism of PAP, and that none of the species studied resembles the human; the rat comes closest, but cannot be considered a particularly good model.