MONOCLONAL DIGOXIN-SPECIFIC ANTIBODIES INDUCE DOSE-DEPENDENT AND AFFINITY-DEPENDENT PLASMA DIGOXIN REDISTRIBUTION IN RATS

The effect of three monoclonal digoxin-specific antibodies on total an d free digoxin plasma disposition was studied in rats in order to dete rmine the role of affinity constant (Ka) and dose. Thirty minutes afte r digoxin infusion, administration of a stoichiometrical dose of the 1 C1O, 6C9 and 9F5 IgG (Ka = 6 10(9), 3.1 10(8) and 2.5 10(7) M(-1), res pectively) resulted in a plasma digoxin increase linearly related to K a. The mean free plasma digoxin was 0.6 +/- 0.4, 7.8 +/- 3.3 and 43 +/ - 22% respectively after 1C10, 6C9, and 9F5 IgG infusion in comparison to 70 +/- 9% in the control group. When the IgG:digoxin ratio increas ed from 1 to 5, plasma digoxin Cmax and AUG(T) also increased as a fun ction of both affinity (Ka) and dose (N), but not linearly. The produc t of NKa defined an immunoreactivity factor that was well fitted to th e digoxin redistribution parameters (Cmax and AUC(T) by a Hill equatio n.