Trial reportJournal of medical toxicology : official journal of the American College of Medical Toxicology2020
The Effect of 4-Methylpyrazole on Oxidative Metabolism of Acetaminophen in Human Volunteers.
Trial report in Journal of medical toxicology : official journal of the American College of Medical Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03878693 (The Effect of 4-methylpyrazole on Oxidative Metabolism of Acetaminophen in Healthy Volunteers), which is not on this map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
The Effect of 4-methylpyrazole on Oxidative Metabolism of Acetaminophen in Healthy Volunteers
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- N-Acetylcysteine for Preventing Acetaminophen-Induced Liver Injury: A Comprehensive Review.Frontiers in pharmacology · 2022Pooled it
- Effects of Fomepizole on Acetaminophen Oxidative Metabolism: A Randomized, Crossover Study in Human Volunteers.Clinical pharmacology and therapeutics · 2026Trial
- The role of fomepizole in acetaminophen-related poisoning: a narrative review.Clinical and experimental emergency medicine · 2026Article
- Reactive oxygen species and peroxynitrite in acetaminophen-induced liver injury: Lipid peroxidation and ferroptosis-like cell death.Ferroptosis and oxidative stress · 2026Article
- Mechanistic insights into hepatic cell type-specific contributions to acetaminophen-induced acute liver injury.World journal of gastroenterology · 2025Review
- Are New Approach Methodologies (NAMs) the Holy Grail of toxicology?Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Evidence that extracellular HSPB1 contributes to inflammation in alcohol-associated hepatitis.Hepatology communications · 2025Article
- N-Acetylcysteine and Hemodialysis in Severe Acetaminophen Toxicity in a 15-Year-Old Adolescent: A Case Report.The American journal of case reports · 2025Article
- 4-Methylpyrazole-mediated inhibition of cytochrome P450 2E1 protects renal epithelial cells, but not bladder cancer cells, from cisplatin toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Acetaminophen should be a critical reference hepatotoxin for evaluating human-relevant in vitro models.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Clinically relevant therapeutic approaches against acetaminophen hepatotoxicity and acute liver failure.Biochemical pharmacology · 2024Review
- Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Comments on: Unveiling the therapeutic promise of natural products in alleviating drug-induced liver injury: Present advancements and future prospects.Phytotherapy research : PTR · 2024Article
- Spatial analysis of renal acetaminophen metabolism and its modulation by 4-methylpyrazole with DESI mass spectrometry imaging.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury.Annual review of pathology · 2024Review
- Massive acetaminophen ingestion managed successfully with N-acetylcysteine, fomepizole, and renal replacement therapy.Clinical nephrology. Case studies · 2024Article
- Assessing Platelet Mitochondrial Dysfunction in a Murine Model of Acute Acetaminophen Toxicity.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2023Article
- Comment on Fomepizole and Acetaminophen Overdose.ACG case reports journal · 2023Article
- Narirutin activates TFEB (transcription factor EB) to protect against Acetaminophen-induced liver injury by targeting PPP3/calcineurin.Autophagy · 2023Article
- Acetaminophen Metabolites on Presentation Following an Acute Acetaminophen Overdose (ATOM-7).Clinical pharmacology and therapeutics · 2023Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
introductionAcetaminophen (APAP) is commonly ingested in both accidental and suicidal overdose. Oxidative metabolism by cytochrome P450 2E1 (CYP2E1) produces the hepatotoxic metabolite, N-acetyl-p-benzoquinone imine. CYP2E1 inhibition using 4-methylpyrazole (4-MP) has been shown to prevent APAP-induced liver injury in mice and human hepatocytes. This study was conducted to assess the effect of 4-MP on APAP metabolism in humans.
methodsThis crossover trial examined the ability of 4-MP to inhibit CYP2E1 metabolism of APAP in five human volunteers. Participants received a single oral dose of APAP 80 mg/kg, both with and without intravenous 4-MP, after which urinary and plasma oxidative APAP metabolites were measured. The primary outcome was the fraction of ingested APAP excreted as total oxidative metabolites (APAP-CYS, APAP-NAC, APAP-GSH).
resultsCompared with APAP alone, co-treatment with 4-MP decreased the percentage of ingested APAP recovered as oxidative metabolites in 24-hour urine from 4.48 to 0.51% (95% CI = 2.31-5.63%, p = 0.003). Plasma concentrations of these oxidative metabolites also decreased.
conclusionsThese results show 4-MP effectively reduced oxidative metabolism of APAP in human volunteers ingesting a supratherapeutic APAP dose.
trial registrationClinicalTrials.gov Identifier: NCT03878693.
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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.