ReviewThe AAPS journal2022
In Vitro to In Vivo Extrapolation Linked to Physiologically Based Pharmacokinetic Models for Assessing the Brain Drug Disposition.
Review in The AAPS journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 26 citations in OpenAlex.
- Advances in Machine Learning-Enhanced PBPK Models for Brain-Targeted Drug Delivery via Nanocarriers: A Comprehensive Review.Journal of functional biomaterials · 2026Review
- Alternative methods for developmental toxicity testing: features, status and future directions.Journal of veterinary science · 2025Review
- Optimization of Brain Penetrant SARM1 Orthosteric Inhibitors and Discovery of Their Paradoxical Subinhibitory Activation.ACS medicinal chemistry letters · 2025Article
- Beyond ADME: The Endogenous Functions of Drug Transporters and Its Impact on Human Disease.Pharmaceutics · 2025Review
- The In Vitro Pharmacokinetics of Medicinal Plants: A Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- 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
- Article
- Digital twin-enhanced three-organ microphysiological system for studying drug pharmacokinetics in pregnant women.Frontiers in pharmacology · 2025Article
- Pharmacokinetics of cannabidiol, (-)-Frontiers in veterinary science · 2025Article
- The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects.International journal of molecular sciences · 2024Review
- Applicability of MDR1 Overexpressing Abcb1KO-MDCKII Cell Lines for Investigating In Vitro Species Differences and Brain Penetration Prediction.Pharmaceutics · 2024Article
- Application of a new MDCKII-MDR1 cell model to measure the extent of drug distribution in vitro at equilibrium for prediction of in vivo unbound brain-to-plasma drug distribution.Fluids and barriers of the CNS · 2024Article
- Uptake Transporters at the Blood-Brain Barrier and Their Role in Brain Drug Disposition.Pharmaceutics · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug development for the central nervous system (CNS) is a complex endeavour with low success rates, as the structural complexity of the brain and specifically the blood-brain barrier (BBB) poses tremendous challenges. Several in vitro brain systems have been evaluated, but the ultimate use of these data in terms of translation to human brain concentration profiles remains to be fully developed. Thus, linking up in vitro-to-in vivo extrapolation (IVIVE) strategies to physiologically based pharmacokinetic (PBPK) models of brain is a useful effort that allows better prediction of drug concentrations in CNS components. Such models may overcome some known aspects of inter-species differences in CNS drug disposition. Required physiological (i.e. systems) parameters in the model are derived from quantitative values in each organ. However, due to the inability to directly measure brain concentrations in humans, compound-specific (drug) parameters are often obtained from in silico or in vitro studies. Such data are translated through IVIVE which could be also applied to preclinical in vivo observations. In such exercises, the limitations of the assays and inter-species differences should be adequately understood in order to verify these predictions with the observed concentration data. This report summarizes the state of IVIVE-PBPK-linked models and discusses shortcomings and areas of further research for better prediction of CNS drug disposition. Graphical abstract.
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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.