Reversal of desipramine toxicity in rats using drug-specific antibody Fab' fragment: effects on hypotension and interaction with sodium bicarbonate.
The effect of drug-specific antibody Fab' fragment on desipramine (DMI) toxicity was studied in anesthetized rats to determine 1) whether DMI-induced hypotension can be reversed, and 2) whether the effect of this Fab' fragment can be enhanced by the concurrent administration of hypertonic NaHCO3. DMI (60 mg/kg) was administered i.p. to produce marked hypotension. Antitricyclic antidepressant (TCA) Fab' (molar Fab'/DMI ratio = 0.11) or control Fab' was administered 15 min later as a 10 min i.v. infusion. The mean arterial pressure was higher at the end of anti-TCA Fab' infusion than after control Fab' (58 +/- 8 vs. 17 +/- 7 mm Hg, P less than .001). In a second protocol, DMI (30 mg/kg) was administered to prolong QRS duration. Anti-TCA Fab' alone (molar Fab'/DMI ratio = 0.09) and NaHCO3 alone both reduced QRS prolongation compared to control treatment, and combined therapy was more effective than either one alone. In both protocols, anti-TCA Fab' markedly increased the total DMI concentration and the bound fraction of DMI in serum, but did not alter the unbound DMI concentration. In the low DMI dose protocol, anti-TCA Fab' also reduced the cardiac DMI concentration. Concurrent treatment with anti-TCA Fab' and NaHCO3 substantially increased urinary DMI and anti-TCA Fab' excretion compared to treatment with anti-TCA Fab' alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Brunn
G J
GJ
Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota.
Keyler
D E
DE
Pond
S M
SM
Pentel
P R
PR
D000818:Animals; D001639:Bicarbonates / Q000008:administration & dosage / Q000494:pharmacology*; D003891:Desipramine / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D004357:Drug Synergism; D004562:Electrocardiography; D007022:Hypotension / Q000139:chemically induced / Q000517:prevention & control*; D007140:Immunoglobulin Fab Fragments / Q000032:analysis / Q000276:immunology*; D008297:Male; D051381:Rats; D012964:Sodium / Q000008:administration & dosage / Q000494:pharmacology*; D017693:Sodium Bicarbonate
D001639:Bicarbonates; D007140:Immunoglobulin Fab Fragments; D017693:Sodium Bicarbonate; D012964:Sodium; D003891:Desipramine