ArticleEuropean journal of drug metabolism and pharmacokinetics2016
Physiologically based modeling of the pharmacokinetics of acetaminophen and its major metabolites in humans using a Bayesian population approach.
Article in European journal of drug metabolism and pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Simultaneous Ivabradine Parent-Metabolite PBPK/PD Modelling Using a Bayesian Estimation Method.The AAPS journal · 2020Trial
- A systems pharmacology model for paracetamol overdose and treatment.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Estimation of species- and sex-specific PFAS pharmacokinetics in mice, rats, and non-human primates using a Bayesian hierarchical methodology.Toxicology and applied pharmacology · 2025Article
- Perioperative Acetaminophen Dosing in Obese Children.Children (Basel, Switzerland) · 2023Review
- Well-tempered MCMC simulations for population pharmacokinetic models.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Physiologically Based Pharmacokinetic Modeling to Characterize Acetaminophen Pharmacokinetics and N-Acetyl-p-Benzoquinone Imine (NAPQI) Formation in Non-Pregnant and Pregnant Women.Clinical pharmacokinetics · 2020Article
- Ontogeny of Hepatic Sulfotransferases and Prediction of Age-Dependent Fractional Contribution of Sulfation in Acetaminophen Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Population pharmacokinetic reanalysis of a Diazepam PBPK model: a comparison of Stan and GNU MCSim.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Paracetamol metabolism, hepatotoxicity, biomarkers and therapeutic interventions: a perspective.Toxicology research · 2018Review
- Applying a Global Sensitivity Analysis Workflow to Improve the Computational Efficiencies in Physiologically-Based Pharmacokinetic Modeling.Frontiers in pharmacology · 2018Article
- Characterizing the Effects of Race/Ethnicity on Acetaminophen Pharmacokinetics Using Physiologically Based Pharmacokinetic Modeling.European journal of drug metabolism and pharmacokinetics · 2017Article
- Translational learning from clinical studies predicts drug pharmacokinetics across patient populations.NPJ systems biology and applications · 2017Article
- Physiologically Based Pharmacokinetic Model of Rifapentine and 25-Desacetyl Rifapentine Disposition in Humans.Antimicrobial agents and chemotherapy · 2016Article
- Acetaminophen-inducedToxicology research · 2016Article
- A novel approach for estimating ingested dose associated with paracetamol overdose.British journal of clinical pharmacology · 2016Article
- Advances in Engineered Liver Models for Investigating Drug-Induced Liver Injury.BioMed research international · 2016Review
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Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The principal aim of this study was to develop, validate, and demonstrate a physiologically based pharmacokinetic (PBPK) model to predict and characterize the absorption, distribution, metabolism, and excretion of acetaminophen (APAP) in humans. A PBPK model was created that included pharmacologically and toxicologically relevant tissue compartments and incorporated mechanistic descriptions of the absorption and metabolism of APAP, such as gastric emptying time, cofactor kinetics, and transporter-mediated movement of conjugated metabolites in the liver. Through the use of a hierarchical Bayesian framework, unknown model parameters were estimated using a large training set of data from human pharmacokinetic studies, resulting in parameter distributions that account for data uncertainty and inter-study variability. Predictions from the model showed good agreement to a diverse test set of data across several measures, including plasma concentrations over time, renal clearance, APAP absorption, and pharmacokinetic and exposure metrics. The utility of the model was then demonstrated through predictions of cofactor depletion, dose response of several pharmacokinetic endpoints, and the relationship between APAP biomarker levels in the plasma and those in the liver. The model addressed several limitations in previous PBPK models for APAP, and it is anticipated that it will be useful in predicting the pharmacokinetics of APAP in a number of contexts, such as extrapolating across doses, estimating internal concentrations, quantifying population variability, assessing possible impacts of drug coadministration, and, when coupled with a suitable pharmacodynamic model, predicting toxicity.
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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.