Interaction of ethanol with acetaminophen metabolism in the baboon.

To evaluate the effects of ethanol on acetaminophen metabolism and toxicity, twelve female baboons were studied using three experimental designs. In the first one, animals fed ethanol chronically and their pair-fed controls received acetaminophen intravenously (40 mg/kg), and drug metabolism was studied for 6 hr in blood and urine. Elimination of acetaminophen from plasma was accelerated significantly in baboons fed alcohol chronically, and urinary excretion of mercapturic acid conjugate was increased. In the second, the experiments were repeated with the addition of ethanol infusion (120-160 mg/kg/hr). During ethanol infusion, elimination of acetaminophen from plasma was still accelerated significantly in baboons fed alcohol chronically. In the third experimental design, four pairs of baboons fed an alcohol or an isocaloric control liquid diet received, in addition, acetaminophen (85 mg/kg/day) in their respective liquid diets for 2 weeks. Liver histology was studied before and after acetaminophen feeding; SGPT, SGOT, SGDH, acetaminophen blood levels and acetaminophen urinary metabolites were also assessed. No morphological or functional liver alterations were found after chronic acetaminophen treatment, and urinary excretion of mercapturic acid conjugate was not increased in baboons fed alcohol chronically. Thus, our results in primates confirm that chronic ethanol consumption increases, whereas acute ethanol administration decreases, the excretion of mercapturic acid conjugate. When acute and chronic ethanol administration were combined, the effects tended to cancel each other out. A dose of acetaminophen which maintained blood levels similar to those recommended for humans did not produce deleterious effects in baboons drinking alcohol.