ReviewThe AAPS journal2013
Physiologically based pharmacokinetic modelling of drug penetration across the blood-brain barrier--towards a mechanistic IVIVE-based approach.
Review in The AAPS journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed.
- Advances in Machine Learning-Enhanced PBPK Models for Brain-Targeted Drug Delivery via Nanocarriers: A Comprehensive Review.Journal of functional biomaterials · 2026Review
- Indole-Derived Compounds as Redox-Modulators: Antioxidant Mechanisms in Neuronal Protection.Molecules (Basel, Switzerland) · 2026Review
- JAK/STAT signaling pathway inhibitors in neurodegenerative diseases: current status and future perspectives.Frontiers in aging neuroscience · 2026Review
- Prediction Models for Brain Distribution of Drugs Based on Biomimetic Chromatographic Data.Molecules (Basel, Switzerland) · 2022Article
- IVIVE: Facilitating the Use ofToxics · 2022Review
- Exploration of the Plausible Mechanism of Ethambutol Induced Ocular Toxicity by Using Proteomics Informed Physiologically Based Pharmacokinetic (PBPK) Modeling.Pharmaceutical research · 2022Article
- Brain Distribution of Drugs: Brain Morphology, Delivery Routes, and Species Differences.Handbook of experimental pharmacology · 2022Article
- Advances in Non-Animal Testing Approaches towards Accelerated Clinical Translation of Novel Nanotheranostic Therapeutics for Central Nervous System Disorders.Nanomaterials (Basel, Switzerland) · 2021Review
- Lumbar cerebrospinal fluid-to-brain extracellular fluid surrogacy is context-specific: insights from LeiCNS-PK3.0 simulations.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Molecular and Functional Study of Transient Receptor Potential Vanilloid 1-4 at the Rat and Human Blood-Brain Barrier Reveals Interspecies Differences.Frontiers in cell and developmental biology · 2020Article
- ABC Transporters at the Blood-Brain Interfaces, Their Study Models, and Drug Delivery Implications in Gliomas.Pharmaceutics · 2019Review
- Development of a physiologically based pharmacokinetic model for intravenous lenalidomide in mice.Cancer chemotherapy and pharmacology · 2019Article
- Development of a physiologically-based pharmacokinetic pediatric brain model for prediction of cerebrospinal fluid drug concentrations and the influence of meningitis.PLoS computational biology · 2019Article
- Mind the Gaps: Ontogeny of Human Brain P-gp and Its Impact on Drug Toxicity.The AAPS journal · 2019Review
- Clinical Pharmacokinetics and Pharmacodynamics of Drugs in the Central Nervous System.Clinical pharmacokinetics · 2018Review
- Jumping the Barrier: Modeling Drug Penetration across the Blood-Brain Barrier.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Opioids and the Blood-Brain Barrier: A Dynamic Interaction with Consequences on Drug Disposition in Brain.Current neuropharmacology · 2017Review
- Microdialysis: the Key to Physiologically Based Model Prediction of Human CNS Target Site Concentrations.The AAPS journal · 2017Review
- Importance of Drug Pharmacokinetics at the Site of Action.Clinical and translational science · 2017Review
- Treating disorders of the neonatal central nervous system: pharmacokinetic and pharmacodynamic considerations with a focus on antiepileptics.British journal of clinical pharmacology · 2016Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Predicting the penetration of drugs across the human blood-brain barrier (BBB) is a significant challenge during their development. A variety of in vitro systems representing the BBB have been described, but the optimal use of these data in terms of extrapolation to human unbound brain concentration profiles remains to be fully exploited. Physiologically based pharmacokinetic (PBPK) modelling of drug disposition in the central nervous system (CNS) currently consists of fitting preclinical in vivo data to compartmental models in order to estimate the permeability and efflux of drugs across the BBB. The increasingly popular approach of using in vitro-in vivo extrapolation (IVIVE) to generate PBPK model input parameters could provide a more mechanistic basis for the interspecies translation of preclinical models of the CNS. However, a major hurdle exists in verifying these predictions with observed data, since human brain concentrations can't be directly measured. Therefore a combination of IVIVE-based and empirical modelling approaches based on preclinical data are currently required. In this review, we summarise the existing PBPK models of the CNS in the literature, and we evaluate the current opportunities and limitations of potential IVIVE strategies for PBPK modelling of BBB penetration.
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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.