Reversal of Digitoxin Toxicity and Modification of Pharmacokinetics by Specific Antibodies

Abstract

Advanced digitalis toxicity unresponsive to conventional therapy continues to be an important clinical problem (Smith and Willerson, 1971; Bismuth et al., 1973; Lely and van Enter, 1970). The cardiac glycoside digitoxin is used in about 16%–20% of digitalis-treated patients in the United States (National Prescription Audit) and is in more common use in some European countries such as France, where 96% of a series of 115 patients treated for acute digitalis poisoning had taken digitoxin with a resulting morality of 22% (Bismuth et al., 1973). Cardiac glycoside-specific antibodies or their Fab fragments have been shown to be capable of reversing a number of pharmacologic and toxic effects of digoxin and ouabain (Butler et al., 1973; Smith et al., 1977). Purified Fab fragments of digoxin-specific antibodies have recently been used clinically to reverse intractable hyperkalemia and advanced atrioventricular block following massive suicidal digoxin ingestion (Smith et al., 1976). Due to the high mortality rate associated with overwhelming digitoxin toxicity and the need for more effective therapy, we have undertaken studies with high affinity digitoxin-specific antibodies to determine their effects in an experimental model of lethal digitoxin toxicity. We have also extended earlier studies of Butler et al. (Butler et al., 1977) with digoxin-specific antibodies and Fab fragments to determine how intact antibodies and Fab fragments with high affinity for digitoxin would influence the pharmacokinetics of digitoxin in an animal model.KeywordsIntact AntibodyStable Sinus RhythmPapillary Muscle PreparationTotal Plasma RadioactivityPlasma DigitoxinThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.