Low-dose probenecid selectively inhibits urinary excretion of phenolsulfonphthalein in rats without affecting biliary excretion
Article first published online: 7 DEC 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 6, pages 511–515, June 2013
How to Cite
Shin, Y.-J., Lee, J. H., Oh, J.-H. and Lee, Y.-J. (2013), Low-dose probenecid selectively inhibits urinary excretion of phenolsulfonphthalein in rats without affecting biliary excretion. J. Appl. Toxicol., 33: 511–515. doi: 10.1002/jat.1778
- Issue published online: 22 APR 2013
- Article first published online: 7 DEC 2011
- Manuscript Accepted: 25 OCT 2011
- Manuscript Revised: 20 OCT 2011
- Manuscript Received: 24 JUL 2011
- biliary excretion;
- urinary excretion
Renal organic anion transport systems play an important role in the excretion of anionic drugs and toxic compounds. Probenecid has been used as a potent inhibitor of urinary and biliary excretion of anionic compounds mediated by transporters such as organic anion transporters and multidrug resistance-associated protein 2 (Mrp2). The purpose of this study was to optimize the dose of probenecid required for selective inhibition of urinary excretion of anionic compounds in rats, without inhibition of biliary excretion. Phenolsulfonphthalein (PSP), a model anionic compound that is excreted in urine and bile, was intravenously administered to rats after intraperitoneal injection of different doses of probenecid (0, 0.2, 2, 10, 100, 200 and 400 mg kg−1). Treatment with 100, 200 or 400 mg kg−1 probenecid decreased both renal clearance (CLr) and biliary clearance (CLb) of PSP, whereas 0.2 mg kg−1 probenecid did not have any effect. Probenecid administered at doses of 2 and 10 mg kg−1 decreased only CLr. The median effective doses of probenecid for inhibiting CLr and CLb were 0.925 and 23.9 mg kg−1, respectively. These data suggest that a low dose of probenecid selectively inhibits urinary excretion of PSP that may be mediated by organic anion transporters, without affecting biliary excretion that may be mediated by Mrp2. Copyright © 2011 John Wiley & Sons, Ltd.