Metabolism and disposition of phenazopyridine in rat

Abstract

1. The blood profile, tissue distribution, biliary and urinary excretion, and metabolism of ¹⁴C-phenazopyridine (PAP) was studied in male Wistar rats.

2. Based on the blood profile of ¹⁴C the absorption of PAP from the gastrointestinal tract was rapid; the tt1/2 of elimination was 7.35 h.

3. Biliary excretion was a major route of elimination with 40.7% dose excreted by this route in bile duct-cannulated rats over the 0-8 h period. The predominant metabolite was conjugated 4′-hydroxy-PAP.

4. Liver and kidney showed the highest tissue levels of PAP-derived ¹⁴C, and significant covalent binding was found in these two tissues.

5. The major urinary metabolite of PAP was 4-acetylaminophenol (NAPA) followed in order by 5,4′-dihydroxy-PAP, 5-hydroxy-PAP, 4′-hydroxy-PAP and 2′-hydroxy-PAP; unchanged PAP accounted for <1% dose.

6. Doubling the dose of PAP to 200mg/kg caused a proportionate decrease in urinary NAPA excretion and an increase in 5-hydroxy-PAP.