Acute ethanol administration reduces the antidote effect of N-acetylcysteine after acetaminophen overdose in mice.
1. The combined antidote effect of N-acetylcysteine and ethanol on the toxicity of acetaminophen was investigated. 2. Fed male mice were given acetaminophen i.p. (600 mg kg-1) and after 5 min in addition ethanol i.p. (0.2 ml, 19% v/v), N-acetylcysteine i.p. (1.2 g kg-1, 0.2 ml), N-acetylcysteine + ethanol i.p. (same doses as given individually) or saline i.p. (0.4 ml). Survival rates were determined after 24, 48, 72 and 96 h. 3. In the N-acetylcysteine group the survival rate was 85%. This rate was significantly reduced to 43% in the N-acetylcysteine + ethanol group (P = 0.0001). In the groups given ethanol or saline alone only 7% and 3%, respectively, survived 96 h. 4. The data suggest that the protective effect of N-acetylcysteine on acetaminophen-induced toxicity in fed mice is reduced by concomitant administration of ethanol. This may explain the clinical observation that ingestion of ethanol worsens the prognosis after acetaminophen intoxication.
Department of Medicine A, Rigshospitalet, Copenhagen, Denmark.
K
K
Dalhoff
P B
PB
Hansen
P
P
Ott
S
S
Loft
H E
HE
Poulsen
D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D004334:Drug Administration Schedule; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011041:Poisoning / Q000188:drug therapy
D000082:Acetaminophen; D000431:Ethanol; D000111:Acetylcysteine