Immunopharmacological activity of monoclonal antidigitoxin.
A monoclonal antibody specific to digitoxin was developed and Fab fragments were prepared using the conventional papain method. The affinity constant was determined as 10(9)M-1 and the cross reactivity with digoxin was 2%. The Fab fragments were used for the reversal of acute digitoxin poisoning in rabbits (100% mortality). Fab fragments were administered over a 40 or 80 minute period just after digitoxin infusion. Rabbits treated with specific Fab fragments were protected by a bistoichiometrical dose. Evaluation of plasma digitoxin confirmed that the specific Fab fragments were able to extract and sequestrate digitoxin. The digitoxin-Fab fragment complexes were removed by renal excretion. Our data provide evidence of the benefit of monoclonal Fab fragments specific for digitoxin for the reversal of acute digitoxin poisoning.
INSERM U 26, Hôpital Fernand Widal, Paris, France.
M
M
Urtizberea
M
M
Latour
L
L
Edelman
J
J
Carcagne
J
J
Armand
J M
JM
Scherrmann
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D004074:Digitoxin / Q000276:immunology* / Q000506:poisoning; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D004074:Digitoxin