Metabolism and disposition of phenazopyridine in rat.
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 t1/2 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 200 mg/kg caused a proportionate decrease in urinary NAPA excretion and an increase in 5-hydroxy-PAP.
Drug Toxicology Division, Bureau of Drug Research, Sir F. G. Banting Research Centre, Ottawa, Ontario, Canada.
B H
BH
Thomas
L W
LW
Whitehouse
G
G
Solomonraj
C J
CJ
Paul
D000818:Animals; D001646:Bile / Q000378:metabolism; D001659:Biliary Tract / Q000378:metabolism; D002250:Carbon Radioisotopes; D008297:Male; D010621:Phenazopyridine / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D011506:Proteins; D010621:Phenazopyridine