Redistribution and altered excretion of digoxin in rats receiving digoxin antibodies incorporated in liposomes

Sheep digoxin antibody was incorporated in liposomes, such that its biological activity was retained. Antibody incorporation was dependent on lipid composition of liposomes and was consistently greatest with the phosphatidylcholine/cholesterol/phosphatidic acid (in a 10:2:1 weight ratio) composition as compared to compositions in which the charged lipid was replaced by dicetylphosphate [bis(hexadecanyl)phosphate] or stearoylamine (octadecanylamine). Digoxin antibodies, whether injected free or as antibody‐liposome complexes, bind circulating digoxin in vivo and alter the intravascular, hepatic and splenic distribution of the cardiac glycoside. Administration of free antibody results in an intavascular retention of the digoxin label, whereas liposome‐antibody complexes were able to remove digoxin to the liver and spleen. There appears to be a later small increase in the intravascular digoxin pool in rats receiving liposome‐antibody complexes, which is probably due to the breakdown of digoxin‐antibody‐liposome complexes in the liver and spleen. Excretory studies showed that the kidney is the major route of excretion of [3H]digoxin and its possible metabolites in rats. The liposomal antibody system seems to enhance digoxin elimination over a 72‐h period when compared with the administration of free antibody. If the eliminated digoxin proves to be in a non‐toxic form, such liposome‐antibody preparations may be of use in removing digoxin from the tissues and blood in cases of digoxin overdose. This principal may have value in the treatment of overdose with clinically toxic compounds such as cytotoxic drugs, paraquat and compounds active on the central nervous system.