Effect of hemoperfusion on the pharmacokinetics of digitoxin in dogs.

Abstract

Abstract To determine the pharmacokinetics of digitoxin, five dogs were given 0.15 mg/kg digitoxin intravenously. Serum digitoxin concentrations were measured by 125 l RIA. Pharmacokinetic analysis was performed with a three-compartment model. The mean Vd was 0.81 ± 0.27 (S.D.) L/kg, mean t12 was 6.60 ± 1.97 hr, and mean Clt was 27 ± 11 ml/min. Another five dogs received the same amount of digitoxin and were hemoperfused at a flow of 108 ml/min for 4 hr with a 300 gm Amberlite XAD-4 column. Vd, t12, and Clt values before perfusion were 0.66 ± 0.27 L/kg, 7.09 ± 3.52 hr, and 34 ± 20 ml/min, not significantly different from the values of the first five dogs. In two dogs, digitoxin concentrations became undetectable within 15 min of starting perfusion, and 58.5 μg of digitoxin were recovered from the columns. In the remaining three dogs, the plasma clearance of digitoxin by the columns was 25 ±7 ml/min, and 233 ± 55 μg of digitoxin were recovered. Mean hemoperfusion clearance calculated from the total amount recovered was 19.7 ± 3.9 ml/ min. After perfusion there was an increase in the serum digitoxin concentration. Once the new pseudo-steady state was reached, the serum digitoxin concentration was from 5 to 44 ng/ml less than if hemoperfusion had not been done. The increase in serum digitoxin concentration after hemoperfusion occurred because the central compartment, depleted of digitoxin during hemoperfusion, was refilled from peripheral compartments. In conclusion, 4 hr of resin hemoperfusion nearly doubled the rate of removal of digitoxin from dogs, and a multicompartmental pharmacokinetic model explains the postperfusion increase in serum digitoxin concentrations.