Effects of blockage of urine and/or bile flow on diflunisal conjugation and disposition in rats

Watt J.A. and Dickinson R.G. (1990) Effects of blockage of urine and/or bile flow on diflunisal conjugation and disposition in rats. Xenobiotica, 20 8: 835-845. doi:10.3109/00498259009046897


Author Watt J.A.
Dickinson R.G.
Title Effects of blockage of urine and/or bile flow on diflunisal conjugation and disposition in rats
Journal name Xenobiotica   Check publisher's open access policy
ISSN 0049-8254
Publication date 1990-01-01
Sub-type Article (original research)
DOI 10.3109/00498259009046897
Volume 20
Issue 8
Start page 835
End page 845
Total pages 11
Publisher Informa Healthcare
Subject 3004 Pharmacology
3005 Toxicology
1303 Specialist Studies in Education
2307 Health, Toxicology and Mutagenesis
1300 Biochemistry, Genetics and Molecular Biology
Abstract 1. The effects of surgical blockage of either or both of the urinary and biliary excretion routes on the elimination of diflunisal (DF) and its conjugates were investigated in pentobarbitone-anaesthetized rats given DF at 10mg/kg i.v. 2. In control animals the acyl glucuronide and phenolic glucuronide conjugates were excreted predominantly in bile, whereas the sulphate conjugate was eliminated almost exclusively in urine. 3. Bilateral ureter ligation had little effect on DF elimination, except for accumulation of the sulphate conjugate in plasma. Compensatory biliary excretion did not occur. 4. Total plasma clearance of DF decreased from 1.01 to 0.68 ml/min per kg following bile duct ligation. Plasma concentrations and urinary excretion of the glucuronides were elevated. 5. In rats with blockage of both urinary and biliary excretion routes, total plasma clearance of DF decreased to 0.59 ml/min per kg. Both the sulphate and phenolic glucuronide conjugates accumulated in plasma, whereas the acyl glucuronide peaked at 30 min and then declined in parallel with DF. The latter result indicates systemic instability of DF acyl glucuronide with hydrolytic regeneration of DF as the likely major consequence.
Q-Index Code C1
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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