Effect of Probenecid on the Pharmacokinetics and Pharmacodynamics of Procainamide

Y. W.Francis Lam, Rebecca A. Boyd, Shu K. Chin, Donald Chang, Kathleen M. Giacomini

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Abstract

Renal tubular transport of organic anions and cations is assumed to be mutually exclusive. However, results of a number of in vitro and in vivo studies suggest an interaction between the organic anion, probenecid, and various organic cations in the proximal renal tubule. To evaluate the clinical importance of such an interaction, the authors investigated the pharmacokinetics and pharmacodynamics of procainamide, an organic cation with a low therapeutic index that is excreted in part by active secretion in the proximal tubule, in the presence and absence of probenecid. In a randomized crossover study, six healthy subjects received a single 750‐mg N dose of procainamide, with and without prior probenecid administration (2 g orally). Blood and urine samples were obtained and pharmacokinetic parameters of procainamide were determined in each treatment period. QT intervals were measured from ECG recordings that were obtained at blood collection times for pharmacodynamic evaluation. Coadministration of probenecid did not result in any significant change in the overall disposition of procainamide. In particular, renal clearance was not significantly different (488 ± 95 mL/min without probenecid vs. 478 ± 69 mL/min in the presence of probenecid). Our data suggest an interaction between probenecid and procainamide in the proximal renal tubule does not exit. Reasons for this lack of interaction are discussed. 1991 American College of Clinical Pharmacology

Original languageEnglish (US)
Pages (from-to)429-432
Number of pages4
JournalThe Journal of Clinical Pharmacology
Volume31
Issue number5
DOIs
Publication statusPublished - May 1991

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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