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Related Experiment Videos

Digoxin-specific Fab fragments impair renal function in the rat

R J Moran1, A D Struthers, D S Hewick

  • 1Department of Pharmacology and Clinical Pharmacology, University of Dundee, Ninewells Hospital, UK.

The Journal of Pharmacy and Pharmacology
|October 1, 1994
PubMed
Summary

Digoxin-specific antibody fragments (DSFab) reduced rat glomerular filtration rate (GFR) by approximately one-third. This finding suggests potential renal function impairment in patients receiving DSFab, especially those with pre-existing kidney issues.

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Area of Science:

  • Pharmacology
  • Nephrology
  • Immunology

Background:

  • Digoxin toxicity is a clinical concern, and digoxin-specific antibody fragments (DSFab) are used for its treatment.
  • Renal function is crucial for drug clearance, and patients on digitalis therapy often have impaired renal function.

Purpose of the Study:

  • To investigate the effects of DSFab on renal function and its plasma and urinary disposition in a rat model.
  • To assess the potential impact of DSFab on glomerular filtration rate (GFR).

Main Methods:

  • Rats were administered intravenous DSFab (2 mg kg-1).
  • Urine volume and creatinine clearance were measured over 24 hours.
  • Plasma and urinary creatinine concentrations, elimination half-life, volume of distribution, and plasma clearance of DSFab were determined.

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Main Results:

  • DSFab administration led to a 33% decrease in creatinine clearance, approximating a reduction in GFR.
  • Urine volume also decreased by 34%, though not significantly different from controls.
  • DSFab exhibited an elimination half-life of 178 minutes and significant distribution into extracellular fluid.

Conclusions:

  • A dose of DSFab equivalent to one-fifth of the usual clinical dose significantly reduced GFR in rats.
  • DSFab treatment may exacerbate renal impairment in patients, particularly those with pre-existing kidney conditions.
  • Further studies are warranted to understand the clinical implications of DSFab on renal function in patients.