ArticleDrug metabolism and disposition: the biological fate of chemicals2017
Physiologically Based Pharmacokinetic Model of the CYP2D6 Probe Atomoxetine: Extrapolation to Special Populations and Drug-Drug Interactions.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Utilizing Minimal Physiologically Based Pharmacokinetic Modeling to Bridge Bevacizumab Pharmacokinetics from Adult to Pediatric Patients.The AAPS journal · 2025Article
- Development of PBPK Population Model for End-Stage Renal Disease Patients to Inform OATP1B-, BCRP-, P-gp-, and CYP3A4-Mediated Drug Disposition with Individual Influencing Factors.Pharmaceutics · 2025Article
- MDMA pharmacokinetics: A population and physiologically based pharmacokinetics model-informed analysis.CPT: pharmacometrics & systems pharmacology · 2025Article
- Application of a physiologically based pharmacokinetic model to predict isoniazid disposition during pregnancy.Clinical and translational science · 2023Article
- Personalizing atomoxetine dosing in children with ADHD: what can we learn from current supporting evidence.European journal of clinical pharmacology · 2023Review
- Predicting the correct dose in children: Role of computational Pediatric Physiological-based pharmacokinetics modeling tools.CPT: pharmacometrics & systems pharmacology · 2023Review
- An open-access data set of pig skin anatomy and physiology for modelling purposes.Database : the journal of biological databases and curation · 2022Article
- Physiologically based pharmacokinetic (PBPK) modeling of piroxicam with regard to CYP2C9 genetic polymorphism.Archives of pharmacal research · 2022Article
- The Impact of the CYP2D6 "Enhancer" Single Nucleotide Polymorphism on CYP2D6 Activity.Clinical pharmacology and therapeutics · 2022Article
- Development of a pediatric physiologically-based pharmacokinetic model to support recommended dosing of atezolizumab in children with solid tumors.Frontiers in pharmacology · 2022Article
- PBPK Analysis to Study the Impact of Genetic Polymorphism of NAT2 on Drug-Drug Interaction Potential of Isoniazid.Pharmaceutical research · 2021Article
- Pediatric Drug-Drug Interaction Evaluation: Drug, Patient Population, and Methodological Considerations.Journal of clinical pharmacology · 2021Review
- Assessment of the Utility of Physiologically-based Pharmacokinetic Model for prediction of Pharmacokinetics in Chinese and Japanese Populations.International journal of medical sciences · 2021Article
- Novel Mechanistic PBPK Model to Predict Renal Clearance in Varying Stages of CKD by Incorporating Tubular Adaptation and Dynamic Passive Reabsorption.CPT: pharmacometrics & systems pharmacology · 2020Article
- Mechanistic PBPK Modeling of Urine pH Effect on Renal and Systemic Disposition of Methamphetamine and Amphetamine.The Journal of pharmacology and experimental therapeutics · 2020Article
- Utilization of Physiologically Based Pharmacokinetic Modeling in Clinical Pharmacology and Therapeutics: an Overview.Current pharmacology reports · 2020Review
- Sampling Site Has a Critical Impact on Physiologically Based Pharmacokinetic Modeling.The Journal of pharmacology and experimental therapeutics · 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
- Pitfalls of using numerical predictive checks for population physiologically-based pharmacokinetic model evaluation.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- State-of-the-Art Review on Physiologically Based Pharmacokinetic Modeling in Pediatric Drug Development.Clinical pharmacokinetics · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Physiologically based pharmacokinetic (PBPK) modeling of drug disposition and drug-drug interactions (DDIs) has become a key component of drug development. PBPK modeling has also been considered as an approach to predict drug disposition in special populations. However, whether models developed and validated in healthy populations can be extrapolated to special populations is not well established. The goal of this study was to determine whether a drug-specific PBPK model validated using healthy populations could be used to predict drug disposition in specific populations and in organ impairment patients. A full PBPK model of atomoxetine was developed using a training set of pharmacokinetic (PK) data from CYP2D6 genotyped individuals. The model was validated using drug-specific acceptance criteria and a test set of 14 healthy subject PK studies. Population PBPK models were then challenged by simulating the effects of ethnicity, DDIs, pediatrics, and renal and hepatic impairment on atomoxetine PK. Atomoxetine disposition was successfully predicted in 100% of healthy subject studies, 88% of studies in Asians, 79% of DDI studies, and 100% of pediatric studies. However, the atomoxetine area under the plasma concentration versus time curve (AUC) was overpredicted by 3- to 4-fold in end stage renal disease and hepatic impairment. The results show that validated PBPK models can be extrapolated to different ethnicities, DDIs, and pediatrics but not to renal and hepatic impairment patients, likely due to incomplete understanding of the physiologic changes in these conditions. These results show that systematic modeling efforts can be used to further refine population models to improve the predictive value in this area.
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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.