Effect of a concomitant single dose of ethanol on the hepatotoxicity and metabolism of acetaminophen in mice

A concomitant single dose of ethanol (1 g/kg) protected mice from hepatic injury induced by acetaminophen (250 mg/kg) as evidenced by the lowering of plasma transaminases. Pharmacokinetic studies with [¹⁴C]acetaminophen indicated that ethanol enhanced the initial blood concentrations of radiolabel and its rate of elimination. A tissue distribution study suggested that these effects were probably due to an ethanol-induced inhibition of the biliary clearance of acetaminophen from the blood. Examination of the urinary and biliary metabolites indicated that ethanol inhibited the excretion of the degradation products derived from the glutathione-deactivated hepatotoxic acetaminophen intermediate. The decrease in acetaminophen induced hepatotoxicity was therefore attributed to an inhibitory effect of ethanol on the biotransformation of acetaminophen to the toxic intermediate.