Effects of high dose alpha-1-acid glycoprotein on desipramine toxicity in rats

Tricyclic antidepressants are bound extensively to alpha-1-acid glycoprotein (AAG) in serum. It has been suggested that the extent of drug-protein binding may influence the magnitude of cardiotoxicity associated with tricyclic antidepressant overdose. To study this question, desipramine (DMI), 45 mg/kg, was administered i.p. to anesthetized rats, producing an increase in QRS duration of 86.4 +/- 20.5% and a decrease in systolic blood pressure of 28.1 +/- 13.2%. Groups of six rats then received human AAG, 2.2 g/kg i.v. over 30 min, 4.4 g/kg i.v. over 60 min or control infusions of albumin. The serum AAG concentration increased to 29 times normal after AAG, 2.2 g/kg, and 46 times normal after AAG, 4.4 g/kg. The serum DMI concentration did not change with albumin infusion but increased 4.7-fold (1.9 +/- 0.7 to 9.0 +/- 1.6 micrograms/ml) after AAG, 2.2 g/kg, and 6.7-fold (2.3 +/- 0.5 to 15.7 +/- 7.0 micrograms/ml) after AAG, 4.4 g/kg. AAG infusion at either dose had no effect on systolic blood pressure compared to albumin. Animals treated with AAG, 2.2 g/kg, had less QRS prolongation 30 min after AAG infusion than animals treated with albumin (41 +/- 13% vs. 64 +/- 8%, P less than .01) but no difference in QRS duration was observed between groups after the higher dose (4.4 g/kg) of AAG or albumin. Cardiac DMI concentrations 90 min after AAG or albumin treatments did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)