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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
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.
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.
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.