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 and free digoxin plasma disposition was studied in rats in order to determine the role of affinity constant (Ka) and dose. Thirty minutes after digoxin infusion, administration of a stoichiometrical dose of the 1C1O, 6C9 and 9F5 IgG (Ka = 6 10(9), 3.1 10(8) and 2.5 10(7) M(-1), respectively) resulted in a plasma digoxin increase linearly related to Ka. 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 increased from 1 to 5, plasma digoxin Cmax and AUG(T) also increased as a function of both affinity (Ka) and dose (N), but not linearly. The product of NKa defined an immunoreactivity factor that was well fitted to the digoxin redistribution parameters (Cmax and AUC(T) by a Hill equation.