Reversal of desipramine toxicity in rats with polyclonal drug-specific antibody Fab fragments.
Drug-specific antibodies, or fragments containing their binding site(s), are a potential means of treating drug overdose. Affinity purified polyclonal ovine Fab (TFab) with a high average affinity constant (Ka = 1.4 x 10(10) M-1) for the common tricyclic antidepressants was evaluated as a possible treatment for tricyclic antidepressant toxicity. Groups of eight anesthetized rats received 30 mg/kg body weight of desipramine (DMI) intraperitoneally, followed after 15 minutes by a 10-minute intravenous injection of 3 ml normal saline solution, 2 gm/kg nonspecific Fab as a control (CFab), or 1 or 2 gm/kg TFab (representing a molar ratio of TFab to DMI of 0.11 and 0.22, respectively). The animals were observed for 3 hours. During the initial 15 minutes, serum DMI levels in the four groups reached 2.3 to 2.9 micrograms/ml, the QRS duration increased by 67.5% to 77.9%, and the systolic pressure fell to between 65% and 85% of its initial value. The group given saline solution showed a gradual return of all these parameters toward normal, whereas CFab caused a transient further QRS prolongation. CFab also caused an initial rise in blood pressure, which then fell progressively, and two of the rats died 2 to 3 hours later with hypotension and bradycardia. Serum DMI concentration did not change significantly in either the saline or CFab groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Pentel
P R
PR
Department of Medicine, Hennepin County Medical Center, University of Minnesota Medical School, Minneapolis 55415.
Ross
C A
CA
Landon
J
J
Sidki
A
A
Shelver
W L
WL
Keyler
D E
DE
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001794:Blood Pressure; D003891:Desipramine / Q000097:blood / Q000276:immunology* / Q000633:toxicity*; D004562:Electrocardiography; D004731:Endotoxins / Q000032:analysis; D006339:Heart Rate; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D016019:Survival Analysis
D000906:Antibodies; D004731:Endotoxins; D007140:Immunoglobulin Fab Fragments; D003891:Desipramine