Reversal of digitalis effects by specific antibodies

Abstract

Highly digoxin-specific or ouabain-specific antibodies can readily be obtained by immunizing rabbits or sheep with repeated injections of the glycoside coupled to protein carriers. By virtue of their binding capacity digoxin-specific antibodies are capable of removing digoxin concentrations from red blood cells and renal tissue specimens. As evidenced by various experiments with human erythrocytes and isolated cardiac preparations in vitro, digoxin effects are rapidly reversible in the presence of digoxin-specific antibodies. In vivo antidigoxin antibodies can protect animals from digoxin effects and promptly abolish established toxic effects, associated with marked alterations of digoxin pharmacokinetics. However, due to the large molecular weight, complete antibodies cannot be eliminated via the renal route. The use of antigen-binding (Fab) fragments of digoxin-specific antibodies offer the advantage of rapid renal elimination of bound and inactivated digoxin. So far, due to potential immune reactions, the clinical use of purified digoxin-specific antibodies of Fab fragments is restricted to life-threatening accidental or suicidal digoxin or digitoxin poisoning.