ArticleClinical pharmacology and therapeutics2017
Circulating acetaminophen metabolites are toxicokinetic biomarkers of acute liver injury.
Article in Clinical pharmacology and therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
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Who cites it
11 citing papers in PubMed, 30 citations in OpenAlex.
- Effects of Fomepizole on Acetaminophen Oxidative Metabolism: A Randomized, Crossover Study in Human Volunteers.Clinical pharmacology and therapeutics · 2026Trial
- A metabolomic analysis of thiol response for standard and modified N-acetyl cysteine treatment regimens in patients with acetaminophen overdose.Clinical and translational science · 2021Trial
- NAPQI adducts in patients with selective hypersensitivity to acetaminophen.Frontiers in pharmacology · 2026Article
- Article
- Acetaminophen Metabolites on Presentation Following an Acute Acetaminophen Overdose (ATOM-7).Clinical pharmacology and therapeutics · 2023Observational
- Evaluation of the Association between Single Nucleotide Polymorphisms of Metabolizing Enzymes with the Serum Concentration of Paracetamol and Its Metabolites.Metabolites · 2022Article
- Rapid Detection of Direct Compound Toxicity and Trailing Detection of Indirect Cell Metabolite Toxicity in a 96-Well Fluidic Culture Device for Cell-Based Screening Environments: Tactics in Six Sigma Quality Control Charts.Applied sciences (Basel, Switzerland) · 2022Article
- Acetylcysteine in paracetamol poisoning: a perspective of 45 years of use.Toxicology research · 2019Review
- Are Polymorphisms in Genes Relevant to Drug Disposition Predictors of Susceptibility to Drug-Induced Liver Injury?Pharmaceutical research · 2017Review
- Should we treat very large paracetamol overdose differently?British journal of clinical pharmacology · 2017Article
- Intestinal deguelin drives resistance to acetaminophen-induced hepatotoxicity in female mice.Gut microbesArticle
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Acetaminophen (paracetamol-APAP) is the most common cause of drug-induced liver injury in the Western world. Reactive metabolite production by cytochrome P450 enzymes (CYP-metabolites) causes hepatotoxicity. We explored the toxicokinetics of human circulating APAP metabolites following overdose. Plasma from patients treated with acetylcysteine (NAC) for a single APAP overdose was analyzed from discovery (n = 116) and validation (n = 150) patient cohorts. In the discovery cohort, patients who developed acute liver injury (ALI) had higher CYP-metabolites than those without ALI. Receiver operator curve (ROC) analysis demonstrated that at hospital presentation CYP-metabolites were more sensitive/specific for ALI than alanine aminotransferase (ALT) activity and APAP concentration (optimal CYP-metabolite receiver operating characteristic area under the curve (ROC-AUC): 0.91 (95% confidence interval (CI) 0.83-0.98); ALT ROC-AUC: 0.67 (0.50-0.84); APAP ROC-AUC: 0.50 (0.33-0.67)). This enhanced sensitivity/specificity was replicated in the validation cohort. Circulating CYP-metabolites stratify patients by risk of liver injury prior to starting NAC. With development, APAP metabolites have potential utility in stratified trials and for refinement of clinical decision-making.
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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.