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Pharmacy World and Science

, Volume 15, Issue 4, pp 165–170 | Cite as

Probenecid inhibits the renal clearance and renal glucuronidation of nalidixic acid

  • T. B. Vree
  • M. Van den Biggelaar-Martea
  • E. W. J. Van Ewijk-Beneken Kolmer
  • Y. A. Hekster
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Abstract

The aim of this pilot study was to demonstrate the possible inhibitory effect of probenecid on the renal glucuronidation and on the renal clearance of nalidixic acid in a human volunteer. Under acidic urine conditions, hardly any nalidixic acid is excreted unchanged (0.2%). It is excreted as acyl glucuronide (53.4%), 7-hydroxymethylnalidixic acid (10.0%), the latter's acyl glucuronide 30.9%, and 7-carboxynalidixic acid (4.2%). Under probenecid co-medication the renal glucuronidation of nalidixic acid is reduced from 53% to 16%; the renal clearance of both nalidixic acid and 7-hydroxymethylnalidixic acid are reduced (p <0.001); the intrinsict 1/2 of the metabolite 7-hydroxymethylnalidixic acid increased from 0.48 h to 4.24 h. The amount of acyl glucuronidation of 7-hydroxymethylnalidixic acid was not altered. Thein vitro protein binding of both acyl glucuronides was increased, while no effect on the unconjugated compounds was seen. Nalidixic acid had no effect on the maximal renal excretion rate of probenecid acyl glucuronide.

Keywords

Clearance Drug interactions Glucuronates Kidney Metabolism Nalidixic acid Probenecid 

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Copyright information

© Periodicals Service Company 1993

Authors and Affiliations

  • T. B. Vree
    • 1
  • M. Van den Biggelaar-Martea
    • 1
  • E. W. J. Van Ewijk-Beneken Kolmer
    • 1
  • Y. A. Hekster
    • 1
  1. 1.Department of Clinical Pharmacy, Sint Radboud HospitalUniversity of NijmegenGA NijmegenThe Netherlands

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