The effect of immunization with digoxin-specific antibodies on digoxin disposition in the mouse

After intravenous dosing, digoxin was rapidly distributed to tissues, with a distribution half-life of 3.0 min. The highest digoxin concentrations at 1 hr post dosing were found in lymph nodes, adrenals, gallbladder (including contents), liver and kidney respectively. Digoxin concentrations in the heart, spleen, brain, lung, skeletal muscle and fat were similar to, or lower than, those in the plasma. The apparent volume of distribution (AVd) was 1 l/kg, and the plasma elimination half-life and clearance (Cl) 2.8 hr and 0.25 l/kg per hr respectively. When digoxin was given one day after passive immunization with digoxin-specific immunoglobulin G (IgG) or Fab fragments the respective plasma digoxin concentrations were elevated some 26- and 5-fold respectively compared with control values. Consequently there were reductions in AVd (93 and 32%) and Cl (94 and 50%). The effect of IgG treatment on clearance was still apparent when the hapten was given up to 14 days after immunization, while the weaker effect of Fab-treatment was less persistent. Although tissue digoxin concentrations were slightly lower in the immunised mice, it was only in the lymph nodes at 10 and 14 days after IgG treatment that the reduction in hapten concentration was statistically significant.