ArticleClinical pharmacokinetics2016
Development of a Physiologically Based Pharmacokinetic/Pharmacodynamic Model to Predict the Impact of Genetic Polymorphisms on the Pharmacokinetics and Pharmacodynamics Represented by Receptor/Transporter Occupancy of Central Nervous System Drugs.
Article in Clinical pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
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- Physiologically Based Pharmacokinetic (PBPK) Modeling of Antidepressants: A Scoping Review of Existing Models, Applications, and Software Tools.Clinical pharmacokinetics · 2026Article
- Optimizing ribociclib dosing in breast cancer with brain metastasis patients using a physiologically based pharmacokinetic model.BMC cancer · 2026Article
- Article
- Dose Adjustment of Quetiapine and Aripiprazole for Pregnant Women Using Physiologically Based Pharmacokinetic Modeling and Simulation.Clinical pharmacokinetics · 2021Article
- Effect of CYP3A4 Inhibitors and Inducers on Pharmacokinetics and Pharmacodynamics of Saxagliptin and Active Metabolite M2 in Humans Using Physiological-Based Pharmacokinetic Combined DPP-4 Occupancy.Frontiers in pharmacology · 2021Article
- Physiologically-Based Pharmacokinetic Models for CYP1A2 Drug-Drug Interaction Prediction: A Modeling Network of Fluvoxamine, Theophylline, Caffeine, Rifampicin, and Midazolam.CPT: pharmacometrics & systems pharmacology · 2019Article
- Physiologically Based Modeling Approach to Predict Dopamine D2 Receptor Occupancy of Antipsychotics in Brain: Translation From Rat to Human.Journal of clinical pharmacology · 2019Article
- Clinical Pharmacokinetics and Pharmacodynamics of Drugs in the Central Nervous System.Clinical pharmacokinetics · 2018Review
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
backgroundGenetic polymorphisms are major determinants of individual variability in a drug's efficacy and safety, which is one of the main challenges in current clinical practice and drug development. The aim of this work was to develop a physiologically based pharmacokinetic (PBPK)/pharmacodynamic (PD) model to predict changes in the PK parameters associated with genetic polymorphisms and the impact of these changes on drugs' PD effect.
methodsWe developed PBPK models for two central nervous system (CNS) medications, namely quetiapine and fluvoxamine that are substrates for polymorphic enzymes by incorporating the corresponding alterations in the enzyme activity and/or abundance. Then, the PBPK models were linked to PD models to predict the influence of these changes on the drugs' PD effect.
resultsApplication of the PBPK models for prediction of phenotypic differences in the PKs compared favorably with reported clinical data. In addition, the PBPK/PD models were able to describe the relationship between the drugs' PD effect and their unbound fractions in the brain and predict changes in receptor/transporter occupancy percentages, obtained from positron emission tomography occupancy studies, associated with genetic variations.
conclusionsThis work provides a simplified approach to predict the influence of genetic polymorphisms on the PK parameters and associated PD effect for CNS drugs. The impact of these polymorphisms on the drugs' PD requires further in vivo validation.
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