ReviewThe AAPS journal2012
Physiologically based pharmacokinetic modeling to investigate regional brain distribution kinetics in rats.
Review in The AAPS journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
51 citing papers in PubMed, 114 citations in OpenAlex.
- Intranasal drug delivery to the brain for neurodegenerative diseases: Current efforts and challenges in delivery platforms and modeling.Advanced drug delivery reviews · 2026Review
- Pharmacokinetics and concentration-behavioral effect relationships differ between brain subcompartments.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Next-generation biomedical nanorobots: active design, intelligent control, and translational opportunities in regenerative and minimally invasive medicine.Journal of nanobiotechnology · 2026Review
- Quantitative comparison of methods for widespread delivery of small molecules across the blood-brain barrier.Communications biology · 2026Article
- 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
- Interspecies Brain PBPK Modeling Platform to Predict Passive Transport through the Blood-Brain Barrier and Assess Target Site Disposition.Pharmaceutics · 2024Article
- 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
- Drug Repurposing, a Fast-Track Approach to Develop Effective Treatments for Glioblastoma.Cancers · 2022Review
- Unbound Brain-to-Plasma Partition Coefficient, KPharmaceutical research · 2022Article
- Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators.Nature reviews. Neuroscience · 2022Review
- In Vitro to In Vivo Extrapolation Linked to Physiologically Based Pharmacokinetic Models for Assessing the Brain Drug Disposition.The AAPS journal · 2022Review
- In Vivo Studies of Drug BBB Transport: Translational Challenges and the Role of Brain Imaging.Handbook of experimental pharmacology · 2022Article
- Investigating brain uptake of a non-targeting monoclonal antibody after intravenous and intracerebroventricular administration.Frontiers in pharmacology · 2022Article
- Brain Distribution of Drugs: Pharmacokinetic Considerations.Handbook of experimental pharmacology · 2022Article
- Understanding Drug Delivery to the Brain Using Liposome-Based Strategies: Studies that Provide Mechanistic Insights Are Essential.The AAPS journal · 2021Review
- 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 Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions.Pharmaceutics · 2021Review
- Impact of CNS Diseases on Drug Delivery to Brain Extracellular and Intracellular Target Sites in Human: A "WHAT-IF" Simulation Study.Pharmaceutics · 2021Article
- SPARC Aggravates Blood-Brain Barrier Disruption via IntegrinOxidative medicine and cellular longevity · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the major challenges in the development of central nervous system (CNS)-targeted drugs is predicting CNS exposure in human from preclinical data. In this study, we present a methodology to investigate brain disposition in rats using a physiologically based modeling approach aiming at improving the prediction of human brain exposure. We specifically focused on quantifying regional diffusion and fluid flow processes within the brain. Acetaminophen was used as a test compound as it is not subjected to active transport processes. Microdialysis probes were implanted in striatum, for sampling brain extracellular fluid (ECF) concentrations, and in lateral ventricle (LV) and cisterna magna (CM), for sampling cerebrospinal fluid (CSF) concentrations. Serial blood samples were taken in parallel. These data, in addition to physiological parameters from literature, were used to develop a physiologically based model to describe the regional brain pharmacokinetics of acetaminophen. The concentration-time profiles of brain ECF, CSF(LV), and CSF(CM) indicate a rapid equilibrium with plasma. However, brain ECF concentrations are on average fourfold higher than CSF concentrations, with average brain-to-plasma AUC(0-240) ratios of 121%, 28%, and 35% for brain ECF, CSF(LV), and CSF(CM), respectively. It is concluded that for acetaminophen, a model compound for passive transport into, within, and out of the brain, differences exist between the brain ECF and the CSF pharmacokinetics. The physiologically based pharmacokinetic modeling approach is important, as it allowed the prediction of human brain ECF exposure on the basis of human CSF concentrations.
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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.