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Paracetamol hepatotoxicity: A built‐in antidote?
Author(s) -
Williams Roger
Publication year - 1986
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840060438
Subject(s) - methionine , antidote , acetaminophen , pharmacology , analgesic , pharmacokinetics , toxicity , medicine , chemistry , anesthesia , biochemistry , amino acid
The analgesic effect, toxicity and kinetics of oral paracetamol were compared with those of paracetamol + l‐methionine (5:1). The analgesic effect of paracetamol, studied in the Randall‐Selitto test in rats, was not changed by methionine: ED 50 was 94.6 mg/kg without methionine and 94.1 mg/kg with it. However, methionine reduced the acute toxicity (LD 50 ) of paracetamol by 50% (p < 0.05) in non‐fasted, fasted and phenobarbital‐pre‐treated mice. In a randomized cross‐over study in 10 human volunteers the pharmacokinetics of paracetamol (1,500 mg) was not affected by methionine (300 mg). The absorption of methionine from the combination tablets was rapid, peak concentrations occurred in plasma at 30 min and were 3–4 times higher than after paracetamol tablets not containing methionine. Methionine in products containing paracetamol should increase their safety and be the simplest way to reduce the high mortality in paracetamol overdosage.