Ethanol and production of the hepatotoxic metabolite of acetaminophen in healthy adults.
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Thummel KE, Slattery JT, Ro H, Chien JY, Nelson SD, Lown KE, Watkins PB
Ethanol and production of the hepatotoxic metabolite of acetaminophen in healthy adults.
Clin Pharmacol Ther. 2000 Jun;67(6):591-9. doi: 10.1067/mcp.2000.106574.
- PubMed ID
- 10872641 [ View in PubMed]
- Abstract
BACKGROUND: Recent case reports suggest that consumption of ethanol may increase the risk of liver injury induced by acetaminophen (INN, paracetamol). However, this possibility is at odds with previous clinical studies that showed that acute ethanol ingestion could protect against hepatotoxicity by inhibiting CYP-mediated acetaminophen oxidation. 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. METHODS: Ten healthy volunteers each received a 6-hour intravenous infusion of ethanol (to achieve a blood concentration of 100 mg/dL ethanol) or 5% dextrose in water, administered in random order. Acetaminophen (500 mg) was ingested 8 hours after the end of the infusion. Blood and urine were collected for assessment of formation of N-acetyl-p-benzoquinone imine (NAPQI), the hepatotoxic metabolite of acetaminophen. RESULTS: Mean NAPQI formation was enhanced by 22% (range, 2% to 38%; P < .03) when the acetaminophen dose was given after an ethanol infusion, compared with after 5% dextrose in water infusion. This mean increase was similar in magnitude to that predicted by a mathematical model describing the induction of CYP2E1, the main enzyme catalyzing NAPQI formation, by a mechanism of enzyme stabilization. CONCLUSIONS: Consumption of up to one 750-mL bottle of wine, six 12-ounce cans of beer, or 9 ounces of 80-proof liquor over the course of a single evening modestly increases the fraction of an acetaminophen dose converted to its toxic metabolite, NAPQI, when acetaminophen is ingested soon after ethanol has been cleared from the body. This change in acetaminophen metabolism may present an incremental increase in the risk of acetaminophen hepatotoxicity.
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- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Ethanol Cytochrome P450 2E1 Protein Humans UnknownSubstrateInducerDetails - Drug Interactions
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Drug Interaction Acetaminophen Avoid alcohol. Alcohol may increase the risk of hepatotoxicity.