JPET Celsis microsomes equal better data

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by GUARINO, A. M.
Right arrow Articles by SCHANKER, L. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by GUARINO, A. M.
Right arrow Articles by SCHANKER, L. S.
Journal of Pharmacology And Experimental Therapeutics, Vol. 164, Issue 2, 387-395, 1968
Copyright © 1968 by American Society for Pharmacology and Experimental Therapeutics

BILIARY EXCRETION OF PROBENECID AND ITS GLUCURONIDE

ANTHONY M. GUARINO 1 and LEWIS S. SCHANKER 1

1 Laboratory of Chemical Pharmacology, National Heart institute, National Institutes of Health, Bethesda, Maryland

The carboxylic acid probenecid, administered to rats with ligated renal pedicles, readily appeared in bile as the unchanged drug and as the glucuronide of a metabolite of the drug. Twenty-five percent of a 50 mg/kg i.v. dose and 86% of a 0.1 mg/kg dose of probenecid were excreted in 90 min. The bile/plasma concentration ratio for the unchanged (free) drug was 5.1 to 14.6 at the higher dose and ranged from 87.7 to >919 for the glucuronide. These high values for the glucuronide were the result of its exceedingly low concentrations in the plasma. When the probenecid dose was increased from 22.2 to 50 mg/kg, with a resultant 2.27-fold increase in the plasma level, the proportion excreted in 90 ruin declined by about one-half, from 58% to 25%, but the amount of glucuronide excreted was unchanged (62% vs. 65%). When the dose was decreased to 0.1 mg/kg, however, about 84% appeared in the bile as the glucuronide. The phenolic acid phenolphthalein, given in a 1:1 molar ratio of inhibitor to drug, depressed the biliary concentration of free probenecid more than that of the glucuronide (by 56% vs. 11%). When the inhibitor/drug ratio was increased to 3:1, probenecid excretion decreased 79% while glucuronide excretion decreased 91%. These findings suggest that, at the low dose, phenolphthalein acted primarily on the transport of unchanged probenecid and, at the higher dose, on uridine diphosphate glucuronyl transferase.

Submitted on March 28, 1968
Accepted on August 10, 1968




This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
B. Yang and C. E. Hill
Nifedipine modulation of biliary GSH and GSSG/ conjugate efflux in normal and regenerating rat liver
Am J Physiol Gastrointest Liver Physiol, July 1, 2001; 281(1): G85 - G94.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
S. Yeleswaram, G. M. Pollack, K. L. R. Brouwer, and E. S. Ward
Probenecid-Associated Alterations in Valproic Acid Pharmacokinetics in Rats: Can in Vivo Disposition of Valproate Glucuronide Be Predicted from in Vitro Formation Data?
Drug Metab. Dispos., April 13, 2001; 29(5): 777 - 777.
[Full Text]

Home page
 Drug Metab. Dispos.Home page
E. S. Ward, G. M. Pollack, and K. L. R. Brouwer
Probenecid-Associated Alterations in Valproic Acid Pharmacokinetics in Rats: Can in Vivo Disposition of Valproate Glucuronide Be Predicted from in Vitro Formation Data?
Drug Metab. Dispos., April 13, 2001; 28(12): 1433 - 1439.
[Abstract] [Full Text]

Home page
 ScienceHome page
C. Statham, M. Melancon Jr, and J. Lech
Bioconcentration of xenobiotics in trout bile: a proposed monitoring aid for some waterborne chemicals
Science, August 20, 1976; 193(4254): 680 - 681.
[Abstract] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics.