ArticleFrontiers in pharmacology2022
Physiologically based pharmacokinetic (PBPK) modeling of the role of CYP2D6 polymorphism for metabolic phenotyping with dextromethorphan.
Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- From prior knowledge to data-informed models: a review of Boolean network inference.Briefings in bioinformatics · 2026Review
- Integration of Clinical Pharmacokinetic Database With Compartmental Modeling and Regulatory Data Analysis.Current therapeutic research, clinical and experimental · 2026Article
- Article
- Evaluation of various internal standards for quantification of dextromethorphan and diphenhydramine in plasma: a fatal overdose case of a mid-teenager caused by personally imported and over-the-counter medicines.Forensic toxicology · 2026Article
- A Complete Picture of theInternational journal of molecular sciences · 2025Article
- Dextromethorphan Overdose with Refractory Status Epilepticus and Reversible Cranial Nerve Reflex Loss: A Case Report.The American journal of case reports · 2025Article
- Advancing understanding of human variability through toxicokinetic modeling, in vitro-in vivo extrapolation, and new approach methodologies.Human genomics · 2024Review
- Physiologically based pharmacokinetic modeling to predict the pharmacokinetics of codeine in different CYP2D6 phenotypes.Frontiers in pharmacology · 2024Article
- Pharmacogenomics of Dementia: Personalizing the Treatment of Cognitive and Neuropsychiatric Symptoms.Genes · 2023Review
- Physiologically based pharmacokinetic (PBPK) modeling of the role of CYP2D6 polymorphism for metabolic phenotyping with dextromethorphan.Frontiers in pharmacology · 2022Article
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Authors and funding
3 authors.
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Abstract
The cytochrome P450 2D6 (CYP2D6) is a key xenobiotic-metabolizing enzyme involved in the clearance of many drugs. Genetic polymorphisms in CYP2D6 contribute to the large inter-individual variability in drug metabolism and could affect metabolic phenotyping of CYP2D6 probe substances such as dextromethorphan (DXM). To study this question, we (i) established an extensive pharmacokinetics dataset for DXM; and (ii) developed and validated a physiologically based pharmacokinetic (PBPK) model of DXM and its metabolites dextrorphan (DXO) and dextrorphan O-glucuronide (DXO-Glu) based on the data. Drug-gene interactions (DGI) were introduced by accounting for changes in CYP2D6 enzyme kinetics depending on activity score (AS), which in combination with AS for individual polymorphisms allowed us to model CYP2D6 gene variants. Variability in CYP3A4 and CYP2D6 activity was modeled based on
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