The influence of digoxin antibodies on digoxin disposition and effect: studies in guinea-pigs and HeLa cells.
Pretreatment of guinea-pigs with digoxin-specific Fab (fragment antigen binding) fragments reduced the cardiotoxicity of intravenously infused digoxin (the lethal doses in Fab-treated and control animals were 1.0 and 0.6 mgkg-1, respectively). At death the serum digoxin concentration was elevated 2 fold in the Fab-treated animals, while the tissue concentrations were generally lower. The 30-40% lower cardiac digoxin concentration (seen in whole homogenate and throughout the subcellular fractions examined) was surprising; presumably this reflects a difference from the controls in the proportion of pharmacologically active/inactive digoxin in this organ. Adding digoxin-specific immunoglobulin G or the Fab fragments to HeLa cells before incubation with digoxin, reduced specific digoxin binding (Na pump-bound) slightly more than the non-specific binding. Adding specific antibody after digoxin, however, did not reduce digoxin binding or effect a recovery in Na pump activity. It seems that the protective effect of digoxin-specific antibodies seen in the guinea-pig can to some extent be simulated using HeLa cells. However, this is apparently not so regarding the widely-reported ability of these antibodies to reverse the action of digoxin.
D000818:Animals; D004077:Digoxin / Q000276:immunology / Q000378:metabolism* / Q000633:toxicity; D005260:Female; D006168:Guinea Pigs; D006367:HeLa Cells / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D009206:Myocardium / Q000378:metabolism*; D014018:Tissue Distribution
D007140:Immunoglobulin Fab Fragments; D004077:Digoxin