The kinetics of papillotoxic doses of 3H-N-phenylanthranilic acid in rats.

Abstract

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.

• Authors: A Whittingham, L Delacruz, N J Gregg, A Albores, P Ijomah, P H Bach
• Journal: Renal physiology and biochemistry (Ren Physiol Biochem) 1989 Sep-Dec Vol. 12 Issue 5-6 Pg. 406-12 ISSN: 1011-6524 [Print] Switzerland
• PMID: 2623353 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ortho-Aminobenzoates
• fenamic acid

Topics

• Animals
• Bile (analysis)
• Feces (analysis)
• Kidney (analysis)
• Kidney Papillary Necrosis (chemically induced)
• Muscles (analysis)
• Myocardium (analysis)
• Rats
• Rats, Inbred Strains
• Stomach (analysis)
• Tissue Distribution
• Urinary Bladder (analysis)
• ortho-Aminobenzoates (administration & dosage, pharmacokinetics, toxicity)