The kinetics of papillotoxic doses of 3H-N-phenylanthranilic acid in rats.
N-phenylanthranilic acid (N-PAA; 4 mmol/kg/day p.o.) causes a diffuse renal papillary necrosis and a polyuria in 7 days. A single dose of 3H-N-PAA was widely distributed with second-order elimination kinetics, t1/2 +/- 50 h for stomach, heart, kidney, and bladder and t1/2 greater than or equal to 90 h for liver, spleen, muscle and lung. The estimated plasma t1/2 = 10.2 h, and over 75% was excreted via urine in 36 h and 13% via faeces in 72 h. In chronically cannulated animals 29% of N-PAA-derived material was in bile and 24% in urine at 36 h, which suggests enterohepatic circulation. Bile and urine contained several metabolites but no parent compound. Multiple doses for 8 and 16 days increased urinary N-PAA excretion to 90% in 36 h, but faecal contents decreased to 6-8% in 72 h and plasma t1/2 to less than or equal to 7.5 h.
Whittingham
A
A
Robens Institute of Health and Safety, University of Surrey, Guildford, UK.
Delacruz
L
L
Gregg
N J
NJ
Albores
A
A
Ijomah
P
P
Bach
P H
PH
D000818:Animals; D001646:Bile / Q000032:analysis; D005243:Feces / Q000032:analysis; D007668:Kidney / Q000032:analysis; D007681:Kidney Papillary Necrosis / Q000139:chemically induced*; D009132:Muscles / Q000032:analysis; D009206:Myocardium / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000032:analysis; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000032:analysis; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity
D062367:ortho-Aminobenzoates; C001209:fenamic acid