Trial reportBMC pharmacology & toxicology2014
A randomized, placebo-controlled trial to determine the course of aminotransferase elevation during prolonged acetaminophen administration.
Trial report in BMC pharmacology & toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00743093 (Aminotransferase Trends During Prolonged Therapeutic Acetaminophen Dosing), which is not on this map. Cited by 20 papers.
What it found
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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.
Aminotransferase Trends During Prolonged Therapeutic Acetaminophen Dosing
Who cites it
20 citing papers in PubMed, 47 citations in OpenAlex.
- Cytokeratin-18 is a sensitive biomarker of alanine transaminase increase in a placebo-controlled, randomized, crossover trial of therapeutic paracetamol dosing (PATH-BP biomarker substudy).Toxicological sciences : an official journal of the Society of Toxicology · 2024Trial
- Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing.British journal of clinical pharmacology · 2016Trial
- Modeling and Simulation of Acetaminophen Pharmacokinetics and Hepatic Biomarkers After Overdoses of Extended-Release and Immediate-Release Formulations in Healthy Adults Using the Quantitative Systems Toxicology Software Platform DILIsym.CPT: pharmacometrics & systems pharmacology · 2025Article
- Model-Based Assessment of the Liver Safety Profile of Acetaminophen to Support its Combination Use with Topical Diclofenac in Mild-to-Moderate Osteoarthritis Pain.Pain and therapy · 2024Article
- Genetic variants associated with ALT elevation from therapeutic acetaminophen.Clinical toxicology (Philadelphia, Pa.) · 2022Article
- 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
- Metabolomic markers predictive of hepatic adaptation to therapeutic dosing of acetaminophen.Clinical toxicology (Philadelphia, Pa.) · 2022Article
- Article
- The Genomics of Elevated ALT and Adducts in Therapeutic Acetaminophen Treatment: a Pilot Study.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2021Article
- Liver Enzyme Elevations inThe American journal of tropical medicine and hygiene · 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
- Identification of Serum Biomarkers to Distinguish Hazardous and Benign Aminotransferase Elevations.Toxicological sciences : an official journal of the Society of Toxicology · 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
- Hepatotoxicity risk factors and acetaminophen dose adjustment, do prescribers give this issue adequate consideration? A French university hospital study.European journal of clinical pharmacology · 2019Article
- Long-term adverse effects of paracetamol - a review.British journal of clinical pharmacology · 2018Review
- Biomarkers of drug-induced liver injury: progress and utility in research, medicine, and regulation.Expert review of molecular diagnostics · 2018Review
- Are some people at increased risk of paracetamol-induced liver injury? A critical review of the literature.European journal of clinical pharmacology · 2018Review
- Can paracetamol (acetaminophen) be administered to patients with liver impairment?British journal of clinical pharmacology · 2016Review
- Open, single-blind, double-blind: which peer review process do you prefer?BMC pharmacology & toxicology · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAcetaminophen administration for more than 4 days causes aminotransferase elevation in some subjects. The objective of this randomized, placebo-controlled trial is to describe the course of alanine aminotransferase (ALT) elevation in subjects administered 4 g/day of acetaminophen for at least 16 days.
methodsA randomized, placebo controlled trial of acetaminophen (4 g/day) vs placebo. Subjects were healthy volunteers with normal liver enzymes. The primary outcome was the course of ALT during acetaminophen administration. All subjects were treated for a minimum of 16 days. Subjects with ALT elevation at day 16 were continued on treatment until these elevations resolved up to a maximum of 40 days. Subjects were also evaluated for elevation of INR or serum bilirubin as evidence of hepatic dysfunction.
results157/205 (77%) completed acetaminophen subjects had no ALT elevation or transient elevations that resolved by day 16. Of the 48 subjects who had ALT elevations at study day 16, 47 continued on acetaminophen and had resolution by study day 40. One acetaminophen subject did not have resolution by study day 40, and the course of aminotransferase elevation suggests an alternative cause. One placebo subject had an ALT elevation at day 16 that resolved by day 22. The highest observed ALT among all acetaminophen subjects was 191 IU/L. The mean ALT at day 16 was 4.4 IU/L higher for the acetaminophen than for the placebo group. No subject developed liver dysfunction.
conclusionsA minority of subjects treated with 4 g/day of acetaminophen for 16 days will have low-grade aminotransferase elevations that are not accompanied by liver dysfunction and resolve if administration is continued. TRIALS REGISTRATION: Clintrials.gov NCT00743093 registered August 26, 2008.
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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.