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The Effects of Urine pH and Plasma Protein Binding on the Renal Clearance of Disopyramide

Clinical Pharmacokinetics volume 2, pages 373–383 (1977)Cite this article

Summary

To ascertain whether the renal clearance of disopyramide (pKa = 8.36) is affected by urine pH, the disposition kinetics of disopyramide were compared during excretion of acidic and alkaline urine following both single dose intravenous (2 mg/kg) and oral (5mg/kg) administration to 4 healthy male volunteers. No significant difference was observed in the plasma concentration-time curve of disopyramide. The mean 72 hour recovery of disopyramide and its N-deisopropyl metabolite (MND) in urine was 55.1 and 20.3% of the dose respectively, with no apparent difference between the two routes of administration or pH of urine. Renal clearance of disopyramide was found to vary with time, which is partly the result of a concentration dependent change in plasma protein binding. The unbound fraction of drug in plasma varied from 0.32 to 0.72 between 0.4 to 4μg/ml concentration. However, time-dependent change in renal clearance of disopyramide persists even after correction for plasma protein binding.

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Affiliations

  1. Clinical Pharmacology-Toxicology Center, University of Kansas Medical Center, College of Health Sciences and Hospital, Kansas City, Kansas, 66103, USA

    D. D. Shen &  Daniel L. Azarnoff

  2. Trainee in Clinical Pharmacology, Department of Medicine , University of Kansas Medical Center, College of Health Sciences and Hospital, Kansas City, Kansas, 66103, USA

    J. L. Cunningham

  3. Abbott International Medical Fellow for Japan, Department of Pharmacology, University of Kansas Medical Center, College of Health Sciences and Hospital, Kansas City, Kansas, 66103, USA

    I. Shudo

Authors
  1. J. L. Cunningham
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  2. D. D. Shen
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  3. I. Shudo
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  4. Daniel L. Azarnoff
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Additional information

Supported by grants from Searle Research Laboratories and GM 15957 from the United States Public Health Service.

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Cunningham, J.L., Shen, D.D., Shudo, I. et al. The Effects of Urine pH and Plasma Protein Binding on the Renal Clearance of Disopyramide. Clin Pharmacokinet 2, 373–383 (1977). https://doi.org/10.2165/00003088-197702050-00004

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  • DOI: https://doi.org/10.2165/00003088-197702050-00004

Keywords

  • Renal Clearance
  • Plasma Protein Binding
  • Disopyramide
  • Unbind Fraction
  • International Medical Research