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Pharmacokinetics of bretylium in dogs and the effect of hemoperfusion on elimination.

The pharmacokinetics of bretylium in dogs and the efficacy of hemoperfusion with a resin column in its removal from the body following intravenous administration of bretylium tosylate were investigated. Five mongrel dogs weighing 18-26 kg were given a bolus dose of 15 mg/kg. Serial blood samples were taken for 24 hr. Hemoperfusion, through a resin column, was then initiated and continued for 4 hr under pentobarbital anesthesia. During hemoperfusion, arterial and venous blood samples were collected several times; venous blood samples were then withdrawn for an additional 8 hr. Urine was collected from each dog in three portions for up to 48-54 hr. Pharmacokinetics of bretylium in dogs could be characterized by a two-compartment open model with a distribution half-life of 7 min and biological half-life of 15.9 +/- 1.9 hr. Plasma levels declined rapidly from approximately 20 microgram/ml at 6 min to less than 2 microgram/ml within 1 hr. The ratio of intercompartmental rate constants, k12/k21, was 16.7, and the volume of the central compartment and apparent volume of distribution were 0.245 and 5.22 liter/kg, respectively, indicating a wide distribution of bretylium into the tissues. Plasma dialysis clearance averaged 29.7 ml/min, which is 30% of the total body clearance (98.8 ml/ min). These data suggest that resin hemoperfusion may not be useful in the treatment of bretylium intoxication.