European Journal of Clinical Pharmacology

, Volume 34, Issue 4, pp 423–426 | Cite as

Biliary excretion of diflunisal conjugates in patients with T-tube drainage

  • R. K. Verbeeck
  • R. G. Dickinson
  • S. M. Pond
Short Communications


The urinary and biliary excretion of diflunisal and its glucuronide and sulphate conjugates were studied in 10 patients following cholecystectomy.

Total urinary excretion (0–24 h) was 36.6±16.4% of the 250 mg dose. Biliary excretion (0–24 h) was restricted to the phenolic and acyl glucuronides and accounted for 3.7±2.3% of the dose. An inverse relationship existed between urinary and biliary excretion of diflunisal and its conjugates.

The data indicate that the reduced plasma clearance of diflunisal in patients with renal failure may, at least in part, be due to increased biliary excretion of diflunisal glucuronides followed by hydrolysis in the gut and reabsorption of diflunisal i.e. enterohepatic cycling.

Key words

diflunisal glucuronide/sulphate conjugates T-tube patients biliary excretion 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Dickinson RG, King AR, Verbeeck RK (1987) Elimination of diflunisal and its conjugates in the bile-exteriorized rat. Clin Exp Pharmacol Physiol [Suppl 11]: Abstract 84Google Scholar
  2. Dickinson RG, Kluck RM, Eadie MJ, Hooper WH (1985) Disposition of beta-glucuronidase-resistant “glucuronides” of valproic acid after intrabiliary administration in the rat: Intact absorption, fecal excretion and intestinal hydrolysis. J Pharmacol Exp Ther 233: 214–221Google Scholar
  3. Faed EM (1980) Decreased clearance of diflunisal in renal insufficiency — an alternative explanation. Br J Clin Pharmacol 10: 85–186Google Scholar
  4. Faed EM (1984) Properties of acyl glucuronides: Implications for studies of the pharmacokinetics and metabolism of acidic drugs. Drug Metab Rev 15: 1213–1249Google Scholar
  5. Hirom PC, Milburn P, Smith RL (1976) Bile and urine as complementary pathways for the excretion of foreign organic compounds. Xenobiotica 6: 55–64Google Scholar
  6. Klaassen CD, Watkins JB (1984) Mechanisms of bile formation, hepatic uptake, and biliary excretion. Pharmacol Rev 36: 1–67Google Scholar
  7. Levine WG (1978) Biliary excretion of drugs and other xenobiotics. Ann Rev Pharmacol Toxicol 18: 81–96Google Scholar
  8. Levy G (1979) Decreased body clearance of diflunisal in renal insufficiency — an alternative explanation. Br J Clin Pharmacol 8: 601Google Scholar
  9. Lin JH, Yeh KC, Duggan DE (1985) Effect of enterohepatic circulation on the pharmacokinetics of diflunisal in rats. Drug Metab Dispos 13: 321–326Google Scholar
  10. Loewen GR, McKay G, Verbeeck RK (1986) Isolation and identification of a new major metabolite of diflunisal in man. The sulfate conjugate. Drug Metab Dispos 14: 127–131Google Scholar
  11. Rollins DE, Klaassen CD (1979) Biliary excretion of drugs in man. Clin Pharmacokinet 4: 368–379Google Scholar
  12. Verbeeck RK (1982) Glucuronidation and disposition of drug glucuronides in patients with renal failure. Drug Metab Disp 10: 87–89Google Scholar
  13. Verbeeck RK, Loewen GR (1984) Direct and simultaneous quantitation of diflunisal and its phenolic and acyl glucuronides by HPLC. The Pharmacologist 26: Abstract 234Google Scholar
  14. Verbeeck RK, Loewen GR, MacDonald JI, Ross SG, Herman RJ (1987) Dose-dependent pharmacokinetics of diflunisal in man. Clin Exp Pharmacol Physiol Suppl II: Abstract 83Google Scholar
  15. Verbeeck RK, Tjandramaga TB, Mullie A, Verbesselt R, Verberckmoes R, de Schepper PJ (1979) Biotransformation of diflunisal and renal excretion of its glucuronides in renal insufficiency. Br J Clin Pharmacol 7: 273–282Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • R. K. Verbeeck
    • 1
  • R. G. Dickinson
    • 2
  • S. M. Pond
    • 1
  1. 1.Department of Medicine, University of QueenslandPrincess Alexandra HospitalBrisbaneAustralia
  2. 2.Department of Medicine, University of QueenslandRoyal Brisbane HospitalBrisbaneAustralia

Personalised recommendations