ArticleEuropean journal of drug metabolism and pharmacokinetics2017
Characterizing the Effects of Race/Ethnicity on Acetaminophen Pharmacokinetics Using Physiologically Based Pharmacokinetic Modeling.
Article in European journal of drug metabolism and pharmacokinetics, 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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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Polymorphic Expression of UGT1A9 is Associated with Variable Acetaminophen Glucuronidation in Neonates: A Population Pharmacokinetic and Pharmacogenetic Study.Clinical pharmacokinetics · 2018Trial
- Genetically Predicted Use of Common Analgesics and Risk of Chronic Obstructive Pulmonary Disease: A Bidirectional Mendelian Randomization Study.International journal of chronic obstructive pulmonary disease · 2026Article
- Evaluation of the PK/PD Changes on MASLD-Related Population-An Example From Simultaneous Acetaminophen Parent-Metabolite PBPK/PD Modeling.CPT: pharmacometrics & systems pharmacology · 2025Article
- 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
- Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy.Frontiers in pharmacology · 2023Article
- Expression of CYP450 enzymes in human fetal membranes and its implications in xenobiotic metabolism during pregnancy.Life sciences · 2022Article
- A Bayesian population physiologically based pharmacokinetic absorption modeling approach to support generic drug development: application to bupropion hydrochloride oral dosage forms.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Well-tempered MCMC simulations for population pharmacokinetic models.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- A descriptive study of pain treatment and its follow-up in primary care of elderly patients after orthopaedic care.Journal of pharmaceutical health care and sciences · 2020Article
- Association of antioxidant nutraceuticals and acetaminophen (paracetamol): Friend or foe?Journal of food and drug analysis · 2018Review
- Applying a Global Sensitivity Analysis Workflow to Improve the Computational Efficiencies in Physiologically-Based Pharmacokinetic Modeling.Frontiers in pharmacology · 2018Article
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
BACKGROUND AND
objectivesAcetaminophen (APAP, paracetamol) is currently the principal cause of acute liver failure in both the USA and the UK. However, relatively little is known about the influence of genes and race/ethnicity on the disposition of APAP and the extent to which genetic variation and ethnicity may predispose individuals to a higher risk of APAP-induced hepatotoxicity. The objective of this research was to develop subpopulation-specific physiologically based pharmacokinetic (PBPK) models for two genetically different groups (Western Europeans and East Asians) and then use the models to quantify the difference in absorption, distribution, metabolism, and excretion (ADME) of APAP between these groups.
methodsA comprehensive set of human pharmacokinetic data mined from the literature was divided into two groups based on ethnicity as an indicator of the expected abundance of phenol-metabolizing alleles. Using these datasets and a Bayesian hierarchical framework, subpopulation-specific physiologically based pharmacokinetic models for APAP were developed and tested for the two groups.
resultsModel simulations were in good agreement with experimental data for both time-dependent parent and metabolite concentrations and summary pharmacokinetic parameters. In addition, simulations were conducted to characterize the difference between ADME in these groups with regard to urinary excretion and APAP area under the curve (AUC) in the liver. Although not dramatic at therapeutic dosing levels, these results demonstrated the divergence in the liver-specific APAP concentrations and AUC between the two groups and suggested that differences in glucuronidation capacity may play a role in this disparity.
conclusionsOverall, the models developed in this study, and others created using this type of hierarchical methodology, are expected to be useful in quantifying ADME in a subpopulation-specific manner and reducing prediction uncertainty compared to that from generalized PBPK modeling approaches.
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