Trial reportBritish journal of clinical pharmacology2016
Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing.
Trial report in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Urinary Acetaminophen Metabolites and Clinical Outcomes in Extremely Premature Infants.American journal of perinatology · 2025Pooled it
- Effects of Fomepizole on Acetaminophen Oxidative Metabolism: A Randomized, Crossover Study in Human Volunteers.Clinical pharmacology and therapeutics · 2026Trial
- Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing.British journal of clinical pharmacology · 2016Trial
- NAPQI adducts in patients with selective hypersensitivity to acetaminophen.Frontiers in pharmacology · 2026Article
- Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Article
- Revolutionizing Precision Medicine: Exploring Wearable Sensors for Therapeutic Drug Monitoring and Personalized Therapy.Biosensors · 2023Review
- Metabolomic Evaluation of N-Acetyl-p-Benzoquinone Imine Protein Adduct Formation with Therapeutic Acetaminophen Administration: Sex-based Physiologic Differences.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2022Article
- Short-Term Safety of Repeated Acetaminophen Use in Patients With Compensated Cirrhosis.Hepatology communications · 2022Article
- Protein Targets of Acetaminophen Covalent Binding in Rat and Mouse Liver Studied by LC-MS/MS.Frontiers in chemistry · 2021Article
- Human multidrug resistance protein 4 (MRP4) is a cellular efflux transporter for paracetamol glutathione and cysteine conjugates.Archives of toxicology · 2020Article
- Adducts Post Acetaminophen Overdose Treated with a 12-Hour vs 20-Hour Acetylcysteine Infusion.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2020Article
- Suspected paracetamol overdose in Monrovia, Liberia: a matched case-control study.BMC pediatrics · 2020Article
- New insights in acetaminophen toxicity: HMGB1 contributes by itself to amplify hepatocyte necrosis in vitro through the TLR4-TRIF-RIPK3 axis.Scientific reports · 2020Article
- Acute Liver Failure of unclear cause? Acetaminophen-protein adducts make the diagnosis.Toxicology communications · 2020Article
- Mitochondrial Damage and Biogenesis in Acetaminophen-induced Liver Injury.Liver research (Beijing, China) · 2019Article
- Acetaminophen Protein Adducts in Hospitalized Children Receiving Multiple Doses of Acetaminophen.Journal of clinical pharmacology · 2019Observational
- Role of extracellular vesicles in release of protein adducts after acetaminophen-induced liver injury in mice and humans.Toxicology letters · 2019Article
- Biomarkers of drug-induced liver injury: progress and utility in research, medicine, and regulation.Expert review of molecular diagnostics · 2018Review
- Acetaminophen Toxicity: Novel Insights Into Mechanisms and Future Perspectives.Gene expression · 2018Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundParacetamol protein adducts (PPA) are a biomarker of paracetamol exposure. PPA are quantified as paracetamol-cysteine (APAP-CYS), and concentrations above 1.1 μmol l(-1) have been suggested as a marker of paracetamol-induced hepatotoxicity. However, there is little information on the range of concentrations observed during prolonged therapeutic dosing.
aimThe aim of the present study was to describe the concentration of PPA in the serum of subjects taking therapeutic doses of paracetamol for at least 16 days.
methodsPreplanned secondary aim of a prospective randomized controlled (placebo vs. 4g day(-1) paracetamol) trial. We measured subjects' serum PPA concentrations every 3 days for a minimum of 16 days. We also measured concentrations on study days 1-3 and 16-25 in subsets of patients. PPA were quantified as APAP-CYS after gel filtration and protein digestion using liquid chromatography/mass spectrometry.
resultsNinety per cent of subjects had detectable PPA after five doses. Median APAP-CYS concentrations in paracetamol-treated subjects increased to a plateau of 0.1 μmol l(-1) on day 7, where they remained. The highest concentration measured was 1.1 μmol l(-1) and two subjects never had detectable PPA levels. PPA were detected in the serum of 78% of subjects 9 days after their final dose.
conclusionsPPA are detectable in the vast majority of subjects taking therapeutic doses of paracetamol. While most have concentrations well below the threshold associated with hepatotoxicity, concentrations may approach 1.1 μmol l(-1) in rare cases. Adducts are detectable after a few doses and can persist for over a week after dosing is stopped.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.