The effect of diazepam in the recovery of rabbits from acute acetaminophenintoxication

We have recently shown that diazepam can reduce mortality of acute iron ove rdose in rats. The mechanism for that effect is not yet defined. Our object ive in the present study was to assess whether diazepam can similarly reduc e mortality of experimental acute acetaminophen intoxication. Survival of r abbits was compared among four groups receiving 3 g/kg (body weight) of ace taminophen (LD,,) orally each, followed by: 1) nothing (group I), 2) one or al dose of 140 mg/kg N-acetylcystein (NAC) an hour later (group II), 3) int ramuscular injection of 7 mg/kg diazepam (group III), 4) intramuscular inje ction of 7 mg/kg diazepam and one oral dose of 140 mg/kg NAC an hour later (group IV). 37.5% of rabbits in group I died after 16 hours, whereas none o f the rabbits in group LU died, (p = 0.04). No animal died during the 96-ho ur observation period in groups Il and IV. Two and four hours post drug adm inistration, acetaminophen plasma concentrations (APC) were significantly l ower among rabbits in group III than in group I(p = 0.0007 and 0.01, respec tively) and significantly lower among rabbits in group IV than in those in group II (p < 0.0001 and p = 0.03, respectively). Acetaminophen plasma conc entrations 2 hours after drug administration were also significantly lower among rabbits in group III than in those in group II (p = 0.0002). Seven an d 24 hours after dosage, APC tended to be higher among rabbits in group III than in those in group I, but not significantly so. Administration of diaz epam without NAC did not prevent liver and renal dysfunction. We conclude t hat early administration of diazepam in acute experimental acetaminophen ov erdose in rabbits reduced APC and mortality, probably by slowing intestinal motility, which resulted in delayed acetaminophen absorption from the gast rointestinal tract.