ArticlePharmaceutical research2017
A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations.
Article in Pharmaceutical research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Intranasal drug delivery to the brain for neurodegenerative diseases: Current efforts and challenges in delivery platforms and modeling.Advanced drug delivery reviews · 2026Review
- Reliability of in vitro data for the mechanistic prediction of brain extracellular fluid pharmacokinetics of P-glycoprotein substrates in vivo; are we scaling correctly?Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Pharmacokinetic Modeling of the Effect of Tariquidar on Ondansetron Disposition into the Central Nervous System.Pharmaceutical research · 2024Article
- Predictions of Bedaquiline Central Nervous System Exposure in Patients with Tuberculosis Meningitis Using Physiologically based Pharmacokinetic Modeling.Clinical pharmacokinetics · 2024Article
- Interspecies Brain PBPK Modeling Platform to Predict Passive Transport through the Blood-Brain Barrier and Assess Target Site Disposition.Pharmaceutics · 2024Article
- Using the LeiCNS-PK3.0 Physiologically-Based Pharmacokinetic Model to Predict Brain Extracellular Fluid Pharmacokinetics in Mice.Pharmaceutical research · 2023Article
- Modeling of the effect of cerebrospinal fluid flow modulation on locally delivered drugs in the brain.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- A Minimal Physiologically Based Pharmacokinetic Model to Characterize CNS Distribution of Metronidazole in Neuro Care ICU Patients.Antibiotics (Basel, Switzerland) · 2022Article
- Unbound Brain-to-Plasma Partition Coefficient, KPharmaceutical research · 2022Article
- Towards a translational physiologically-based pharmacokinetic (PBPK) model for receptor-mediated transcytosis of anti-transferrin receptor monoclonal antibodies in the central nervous system.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- In Vitro to In Vivo Extrapolation Linked to Physiologically Based Pharmacokinetic Models for Assessing the Brain Drug Disposition.The AAPS journal · 2022Review
- In Vitro to In Vivo Extrapolation Linked to Physiologically Based Pharmacokinetic Models for Assessing the Brain Drug Disposition.The AAPS journal · 2022Review
- Brain Distribution of Drugs: Pharmacokinetic Considerations.Handbook of experimental pharmacology · 2022Article
- Lumbar cerebrospinal fluid-to-brain extracellular fluid surrogacy is context-specific: insights from LeiCNS-PK3.0 simulations.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Understanding the brain uptake and permeability of small molecules through the BBB: A technical overview.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
- Modeling the Effect of Binding Kinetics in Spatial Drug Distribution in the Brain.Computational and mathematical methods in medicine · 2021Article
- Pharmacokinetic Modeling of the Impact of P-glycoprotein on Ondansetron Disposition in the Central Nervous System.Pharmaceutical research · 2020Article
- The 3D Brain Unit Network Model to Study Spatial Brain Drug Exposure under Healthy and Pathological Conditions.Pharmaceutical research · 2020Article
- A 3D brain unit model to further improve prediction of local drug distribution within the brain.PloS one · 2020Article
- Improving the Prediction of Local Drug Distribution Profiles in the Brain with a New 2D Mathematical Model.Bulletin of mathematical biology · 2019Article
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Authors and funding
18 authors.
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Abstract
purposePredicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human brain disposition.
methodsA mathematical model consisting of several physiological brain compartments in the rat was developed using rich concentration-time profiles from nine structurally diverse drugs in plasma, brain extracellular fluid, and two cerebrospinal fluid compartments. The effect of active drug transporters was also accounted for. Subsequently, the model was translated to predict human concentration-time profiles for acetaminophen and morphine, by scaling or replacing system- and drug-specific parameters in the model.
resultsA common model structure was identified that adequately described the rat pharmacokinetic profiles for each of the nine drugs across brain compartments, with good precision of structural model parameters (relative standard error <37.5%). The model predicted the human concentration-time profiles in different brain compartments well (symmetric mean absolute percentage error <90%).
conclusionsA multi-compartmental brain pharmacokinetic model was developed and its structure could adequately describe data across nine different drugs. The model could be successfully translated to predict human brain concentrations.
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