PMID: 9180355Jan 1, 1997Paper

Conjugation-deconjugation cycling of diflunisal via beta-glucuronidase catalyzed hydrolysis of its acyl glucuronide in the rat

Life Sciences
F M Brunelle, R K Verbeeck

Abstract

The role of beta-glucuronidase catalyzed hydrolysis of glucuronides on the in vivo disposition kinetics of xenobiotics was studied in the rat. The metabolic disposition kinetics of diflunisal, a compound undergoing transformation to an acyl and phenyl glucuronide, were studied in rats under control conditions and following administration of D-glucaro-1,4-lactone, a potent and specific beta-glucuronidase inhibitor. D-glucaro-1,4-lactone treatment resulted in a significant decrease in beta-glucuronidase activity in plasma, urine, and hepatic microsomes. Total (i.e. urinary and biliary) recovery of the acyl glucuronide following i.v. injection of diflunisal (10 mg/kg) was significantly higher in D-glucaro-1,4-lactone treated rats (41 +/- 3%, n=6) compared to control rats (29 +/- 2%, n=6) whereas for diflunisal phenyl glucuronide this total recovery was very similar in both groups of rats (16.0 +/- 1.0% vs. 18.0 +/- 0.2%, n=6, respectively). The partial clearance of diflunisal associated with the formation of the acyl glucuronide was significantly higher in D-glucaro-1,4-lactone treated rats (0.413 +/- 0.024 ml/min/kg) compared to control animals (0.269 +/- 0.042 ml/min/kg). The partial clearance related to the formation of the phe...Continue Reading

References

Nov 1, 1991·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R G DickinsonA R King
Nov 1, 1989·Therapeutic Drug Monitoring·R G Dickinson, A R King
Dec 1, 1989·Clinical and Experimental Pharmacology & Physiology·R G DickinsonR K Verbeeck
Apr 1, 1989·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A Macfadyen, K J Ho
Nov 15, 1986·Cancer·R M Ward, H L Evans
Jun 1, 1968·Lancet·L OkolicsanyiJ Frei
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Aug 1, 1996·Clinical and Experimental Pharmacology & Physiology·R G Dickinson, A R King

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Citations

Mar 30, 2004·Biochemical and Biophysical Research Communications·Tom S ChanPeter J O'Brien
Oct 31, 1998·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·C J MeunierR K Verbeeck
Jan 6, 2010·Environmental Health Perspectives·Gary Ginsberg, Deborah C Rice
Jun 28, 2017·Journal of Medicinal Chemistry·Yong MaDonglu Zhang
Jan 28, 2003·Therapeutic Drug Monitoring·Maria ShipkovaEberhard Wieland
May 15, 2002·American Journal of Physiology. Endocrinology and Metabolism·Yasumasa GotohYuichi Sugiyama

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