Hemoperfusion removal of digoxin from dogs

Removal of digoxin by XAD-4 hemoperfusion columns was tested after four dogs were given 0.06 mg/kg of digoxin i.v. Dogs were perfused for 4 to 5 hr at a flow of 105 ml/min through a 100 gm XAD-4 column 16 hr after the dose. Pharmacokinetic analysis of digoxin levels was performed with a three-compartment model. The apparent postdistribution t 1/2 was 16.0±2.9 (S.D.) hr and decreased to 7.1±2.1 hr during perfusion. Digoxin perfusion clearance was 46 ml/min. An average of 51 μg of digoxin was recovered from used columns. Plasma clearance of digoxin calculated from the total amount recovered was 127.5±13 ml/min or 2.3 times greater than plasma flow. With the use of ³H-digoxin, canine blood was found to contain 2.5 times as much digoxin as did plasma. After perfusion there was an increase in serum digoxin levels in all dogs. Computer analysis showed that the increase in plasma digoxin levels immediately after hemoperfusion occurred because the central compartment, which was depleted of digoxin during hemoperfusion, was refilled from peripheral compartments. This study demonstrated that (1) XAD-4 hemoperfusion doubles the rate of removal of digoxin from dogs, (2) dog whole blood contains more than twice as much digoxin than does plasma, so that hemoperfusion clearance exceeds plasma flow, and (3) a multicompartmental pharmacokinetic model explains the increase in serum digoxin concentrations observed at the completion of hemoperfusion.