ArticleScientific reports2018
Physiologically based pharmacokinetic modelling of atomoxetine with regard to CYP2D6 genotypes.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Physiologically based pharmacokinetic (PBPK) modelling of tamsulosin related to CYP2D6*10 allele.Archives of pharmacal research · 2021Trial
- Individualized atomoxetine response and tolerability in children with ADHD receiving different dosage regimens: the need for CYP2D6 genotyping and therapeutic drug monitoring to dance together.Translational psychiatry · 2024Article
- Physiologically based pharmacokinetic (PBPK) modeling of pitavastatin in relation to SLCO1B1 genetic polymorphism.Archives of pharmacal research · 2024Article
- Precision pharmacotherapy of atomoxetine in children with ADHD: how to ensure the right dose for the right person?Frontiers in pharmacology · 2024Review
- PBPK modeling to predict the pharmacokinetics of pantoprazole in different CYP2C19 genotypes.Archives of pharmacal research · 2024Article
- Physiologically based pharmacokinetic (PBPK) modeling to predict the pharmacokinetics of irbesartan in different CYP2C9 genotypes.Archives of pharmacal research · 2023Article
- Personalizing atomoxetine dosing in children with ADHD: what can we learn from current supporting evidence.European journal of clinical pharmacology · 2023Review
- [A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder:Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Review
- Physiologically Based Pharmacokinetic Modeling to Describe the CYP2D6 Activity Score-Dependent Metabolism of Paroxetine, Atomoxetine and Risperidone.Pharmaceutics · 2022Article
- Physiologically based pharmacokinetic modelling to predict the pharmacokinetics of metoprolol in different CYP2D6 genotypes.Archives of pharmacal research · 2022Article
- Physiologically based pharmacokinetic (PBPK) modeling of piroxicam with regard to CYP2C9 genetic polymorphism.Archives of pharmacal research · 2022Article
- Effects of CYP2C9*3 and *13 alleles on the pharmacokinetics and pharmacodynamics of glipizide in healthy Korean subjects.Archives of pharmacal research · 2022Article
- Physiologically based pharmacokinetic (PBPK) modeling of meloxicam in different CYP2C9 genotypes.Archives of pharmacal research · 2021Article
- Predictive modeling of aspirin-triggered resolvin D1 pharmacokinetics for the study of Sjögren's syndrome.Clinical and experimental dental research · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Atomoxetine is a norepinephrine reuptake inhibitor indicated in the treatment of attention-deficit/hyperactivity disorder. It is primarily metabolized by CYP2D6 to its equipotent metabolite, 4-hydroxyatomoxetine, which promptly undergoes further glucuronidation to an inactive 4-HAT-O-glucuronide. Clinical trials have shown that decreased CYP2D6 activity leads to substantially elevated atomoxetine exposure and increase in adverse reactions. The aim of this study was to to develop a pharmacologically based pharmacokinetic (PBPK) model of atomoxetine in different CYP2D6 genotypes. A single 20 mg dose of atomoxetine was given to 19 healthy Korean individuals with CYP2D6*wt/*wt (*wt = *1 or *2) or CYP2D6*10/*10 genotype. Based on the results of this pharmacokinetic study, a PBPK model for CYP2D6*wt/*wt individuals was developed. This model was scaled to those with CYP2D6*10/*10 genotype, as well as CYP2D6 poor metabolisers. We validated this model by comparing the predicted pharmacokinetic parameters with diverse results from the literature. The presented PBPK model describes the pharmacokinetics after single and repeated oral atomoxetine doses with regard to CYP2D6 genotype and phenotype. This model could be utilized for identification of appropriate dosages of atomoxetine in patients with reduced CYP2D6 activity to minimize the adverse events, and to enable personalised medicine.
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