Possible Interaction: Acetaminophen and Ethanol

“Urinary endogenous metabolites of trimethylamine-N-oxide, citrate, 3-chlorotyrosine, phenylalanine, glycine, hippurate, and glutarate as well as plasma endogenous metabolites such as lactate, glucose, 3-hydroxyisovalerate, isoleucine, acetylglycine, acetone, acetate, glutamine, ethanol , and isobutyrate responded significantly to APAP dosing in humans.”

“Recent case reports suggest that consumption of ethanol may increase the risk of liver injury induced by acetaminophen (INN, paracetamol).”

“We tested the hypothesis that ethanol ingestion can increase susceptibility to acetaminophen toxicity if acetaminophen ingestion occurs shortly after ethanol is cleared from the body.”

“Simultaneous application of 1,000 mg of acetaminophen and 10% peppermint oil in ethanol solution leads to an additive effect which remains below the significance threshold, however.”

“Nevertheless, the finding that at greater than typical analgesic doses, acetaminophen failed to prevent subjective effects of ethanol is of clinical significance.”

“The gaps are larger and more frequent in ethanol binged animals subsequently treated with APAP.”

“The upregulation of cytochrome CYP2E1 by chronic ethanol use plays a key role in the pathogenesis of ALD and alters the metabolism of other compounds such as acetaminophen and environmental pro-carcinogens.”

“A lower threshold for treatment of paracetamol acetaminophen ) poisoning has been advocated in chronic heavy users of alcohol , based originally on animal studies indicating that chronic alcohol ingestion increased hepatotoxicity.”

“ Acetaminophen (APAP), a widely used over-the-counter analgesic, is known to cause hepatotoxicity when ingested in large quantities in both animals and man, especially when administered after chronic ethanol consumption.”

“At their respective peak in vivo concentrations attained following hepatoprotective doses, both ethanol and 4-MP inhibited the oxidation of APAP in microsomes by 25-30%.”

“By varying the time of ethanol administration relative to APAP in mice (30 min before to 240 min after APAP), it was shown that ethanol must be administered early relative to APAP for hepatoprotection to be maximized.”

“The protective effect of a single dose of ethanol with regard to hepatotoxicity caused by acetaminophen (APAP) can be a consequence of either direct or indirect inhibition of APAP oxidation to its hepatotoxic intermediate (N-acetyl-p-benzoquinoneimine, NAPQI), or augmentation of repair mechanisms following the hepatotoxic insult.”

“… APAP … ethanol is less than half of the apparent inhibition of APAP oxidation reported in clinical studies in which the maximum ethanol concentration would have been … the mouse, inhibition of APAP oxidation to NAPQI in humans appears to be largely indirect, as has been reported previously in the rat.”

“… acetaminophen hepatotoxicity is … rats fed alcohol chronically and acute ethanol has been shown to inhibit the biotransformation of acetaminophen to reactive metabolite(s) by mixed function oxidation, we … that acute ethanol administration decreases acetaminophen-induced hepatotoxicity in rats fed alcohol chronically by inhibiting the enhanced production of toxic metabolites.”