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Pharmacy World and Science

, Volume 15, Issue 5, pp 197–202 | Cite as

Interindividual variation in the capacity-limited renal glucuronidation of probenecid by humans

  • T. B. Vree
  • E. W. J. Van Ewijk-Beneken Kolmer
  • E. W. Wuis
  • Y. A. Hekster
  • M. M. M. Broekman
Articles

Abstract

A dose of 1,000 mg probenecid was administered orally to 14 human volunteers in order to quantify the maximal rate of formation and excretion of probenecid acyl glucuronide in the urine. Probenecid showed dose-dependent pharmacokinetics. Plasma protein binding of probenecid was high, being somewhat higher in males (90.7±1.4%) than in females (87.9±1.4%; p=0.0019). It was shown that probenecid is metabolized by cytochrome P-450 into at least two phase I metabolites. Each of the metabolites accounted for less than 12% of the dose administered; the main metabolite probenecid acyl glucuronide, representing 42.9±13.2% of the dose, was only present in urine and not in plasma. The renal excretion rate-time profile of probenecid acyl glucuronide showed a plateau value in the presence of an acidic urine pH. This plateau value was maintained for about 10 h at the dose of 1,000 mg. The height of the plateau value depended on the individual and varied between 250 and 800μg/min (15–50 mg/h). It was inferred that probenecid acyl glucuronide is formed in the kidney during blood-to-lumen passage through the tubular cells. We conclude that the plateau value in the renal excretion rate of probenecid glucuronide reflects itsVmax of formation.

Keywords

Clearance, renal Glucuronates Metabolism Pharmacokinetics Probenecid Protein binding 

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Copyright information

© Periodicals Service Company 1993

Authors and Affiliations

  • T. B. Vree
    • 1
  • E. W. J. Van Ewijk-Beneken Kolmer
    • 1
  • E. W. Wuis
    • 1
  • Y. A. Hekster
    • 1
  • M. M. M. Broekman
    • 1
  1. 1.Department of Clinical PharmacyAcademic Hospital Nijmegen Sint RadboudGA Nijmegenthe Netherlands

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