Key result
Prior immunization with a digoxin-human serum albumin conjugate increased the digoxin doses causing the first signs of cardiotoxicity and death by 3- and 2.4-fold, respectively, in guinea-pigs.
Why the study?
Does prior immunization with a digoxin-human serum albumin conjugate reduce digoxin cardiotoxicity in guinea-pigs?
Does prior immunization with a digoxin-human serum albumin conjugate reduce digoxin cardiotoxicity in guinea-pigs?
Effect estimate: 3- and 2.4-fold increase
Digoxin-specific active immunization protects against digoxin toxicity in guinea-pigs by reducing drug access to the site of action within the heart.
May attenuate digoxin cardiotoxicity via active immunization in guinea pigs; leaves open human translation and clinical testing.
In guinea-pigs intravenously infused with digoxin, prior immunization using a digoxin-human serum albumin conjugate increased by 3- and 2.4-fold, respectively, the digoxin doses causing the first signs of cardiotoxicity and death. At death, serum digoxin concentration was four times higher in immunized than in control animals. In the immunized guinea-pigs 50% of the serum digoxin was protein bound, presumably mainly to digoxin-specific antibodies, since in the controls the bound fraction was only 1-2%. Generally, tissue digoxin concentrations were not increased to the same extent as the lethal dose, and in the heart and lungs the increase was not significant. With cardiac (ventricle) subcellular fractions, there was no difference between control and immunized animals in the digoxin concentration of the 'microsomal' pellet. This subfraction contains the plasma membrane and the associated sodium pumps which are considered to be the sites at which the pharmacologically active digoxin binds. It seems likely, therefore, that the greater digoxin resistance in the immunized animals can be explained on the basis of reduced drug access to the site of action within the heart.
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Andrews et al. (1986) studied Digoxin toxicity. Digoxin-specific active immunization (digoxin-human serum albumin conjugate) vs. Control animals was evaluated on Digoxin doses causing the first signs of cardiotoxicity and death (3- and 2.4-fold increase). Prior immunization with a digoxin-human serum albumin conjugate increased the digoxin doses causing the first signs of cardiotoxicity and death by 3- and 2.4-fold, respectively, in guinea-pigs.
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