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Editorial |
Departments of
1
Pathology and Laboratory Medicine and ,
2
Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292
a Author for correspondence. Fax 502-852-1771; e-mail rvaldes@louisville.edu.
Digoxin is one of the few therapeutic drugs for which antidotal therapy is available (1) . Administration of Fab fragments has successfully been used to reverse the effects of life-threatening digoxin overdoses for over 20 years. Digoxin-specific Fab fragments are produced by cleaving sheep digoxin-specific IgG with papain to form two Fab fragments (50 000 Da each) and one 50 000-Da Fc fragment (2) . As determined by equilibrium dialysis with one such preparation of Fab fragments, the intrinsic affinity constant for binding of digoxin was 1010 L/mol (3) . Depending on the experimental conditions used (e.g., K+ concentration and type of membrane isolated), the affinity constant for binding of digoxin to its receptor (the sodium pump) has been reported to be in the range 106-108 L/mol (4)(5) . The rationale for using Fab fragments to reduce toxic effects of digoxin is their greater affinity for digoxin when compared with the sodium pump. As a consequence, the extracellular unbound digoxin concentration is lowered, and further equilibration of receptor-bound digoxin with the fluid in the extracellular space leads to the eventual release of digoxin from its receptor sites. The affinity of digitoxin for binding to Fab fragments is 10-fold lower than that of digoxin; however, it is high enough to allow clinical utility of Fab fragments in cases of digitoxin intoxication as well (3) .
The dose of Fab fragments should be approximately equimolar to the
total body digoxin load, which is determined according to the serum
digoxin concentration and/or patient's medical history (6) .
Digibind® (Glaxo Wellcome) is the most common brand of
anti-digoxin Fab fragments used in the United States and worldwide.
Boehringer-Mannheim also produces anti-digoxin Fab fragments intended
for use as an antidote.
References
The following articles in journals at HighWire Press have cited this article:
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G. A. McMillin, W. E. Owen, T. L. Lambert, B. K. De, E. L. Frank, P. R. Bach, T. M. Annesley, and W. L. Roberts Comparable Effects of DIGIBIND and DigiFab in Thirteen Digoxin Immunoassays Clin. Chem., September 1, 2002; 48(9): 1580 - 1584. [Full Text] [PDF] |
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W. Steimer, C. Muller, and B. Eber Digoxin Assays: Frequent, Substantial, and Potentially Dangerous Interference by Spironolactone, Canrenone, and Other Steroids Clin. Chem., March 1, 2002; 48(3): 507 - 516. [Abstract] [Full Text] [PDF] |
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