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.
Dalhoff
K
K
Department of Medicine A, Rigshospitalet, Copenhagen, Denmark.
Hansen
P B
PB
Ott
P
P
Loft
S
S
Poulsen
H E
HE
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