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Studies of the renal excretion of probenecid acyl glucuronide in man

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Summary

The metabolism of probenecid has been investigated in both normal and gouty subjects. To carry out these studies, specific spectrophotometric methods were developed for the measurement of a major metabolite of probenecid, the acyl glucuronide. This conjugate was isolated in semi-pure state and its identity as a mono acyl glucuronide established. Our experiments indicate that about 25% of probenecid is converted to its acyl glucuronide and that only a small amount of the drug is excreted unchanged. About 80% of orally administered14C probenecid could be accounted for in urine, and about half of this was found to consist of metabolites more polar than the parent drug. The renal clearance of probenecid acyl glucuronide was shown to be about 1/3 that of creatinine clearance, whereas the clearance of probenecid was lower. The present findings in man and those of other workers in animals, raise the important question of the possible contribution of these metabolites to the overall pharmacological effects resulting from the administration of probenecid.

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Authors and Affiliations

  1. Department of Medicine, Division of Clinical Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA

    J. M. Perel & P. G. Dayton

  2. Department of Medicine, Mt. Sinai School of Medicine, New York, USA

    T. F. Yü & A. B. Gutman

Authors
  1. J. M. Perel
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  2. P. G. Dayton
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  3. T. F. Yü
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  4. A. B. Gutman
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Additional information

Supported by NIH Grants A-162 and GM-14270; portions of this work were initially carried out under Grant A-4724 at the NYU Research Service, Goldwater Memorial Hospital, New York, N.Y.

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Perel, J.M., Dayton, P.G., Yü, T.F. et al. Studies of the renal excretion of probenecid acyl glucuronide in man. Eur J Clin Pharmacol 3, 106–112 (1971). https://doi.org/10.1007/BF00619303

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  • DOI: https://doi.org/10.1007/BF00619303

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