ArticlePharmaceutical research2020
Impact of In Vitro Passive Permeability in a P-gp-transfected LLC-PK1 Model on the Prediction of the Rat and Human Unbound Brain-to-Plasma Concentration Ratio.
Article in Pharmaceutical research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 17 citations in OpenAlex.
- Simulation-based assessment of the P-glycoprotein expression-activity relationship shows a drug and system dependency.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- A surrogate barrier model for high-throughput blood-brain barrier permeability prediction: integrating LLC-PK1-MOCK/MDR1 Cells and lysosomal trapping correction.Drug delivery · 2025Article
- 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
- Preclinical evaluation of targeted therapies for central nervous system metastases.Disease models & mechanisms · 2024Review
- 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
- Article
- Successful Prediction of Human Steady-State Unbound Brain-to-Plasma Concentration Ratio of P-gp Substrates Using the Proteomics-Informed Relative Expression Factor Approach.Clinical pharmacology and therapeutics · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMore accurate prediction of the extent of drug brain exposure in early drug discovery and understanding potential species differences could help to guide medicinal chemistry and avoid unnecessary animal studies. Hence, the aim of the current study was to validate the use of a P-gp transfected LLC-PK1 model to predict the unbound brain-to-plasma concentration ratio (Kp
methodsMOCK-, Mdr1a- and MDR1-transfected LLC-PK1 monolayers were applied in a transwell setup to quantify the bidirectional transport for 12 specific P-gp substrates, 48 UCB drug discovery compounds, 11 compounds with reported rat in situ brain perfusion data and 6 compounds with reported human Kp
resultsA 10-fold difference between in vitro and in vivo passive permeability was observed. Incorporation of the differences between in vitro and in vivo passive permeability and P-gp expression levels resulted in an improved prediction of rat (AAFE 2.17) and human Kp
conclusionsWe have succesfully validated a methodology to use a P-gp overexpressing LLC-PK1 cell line to predict both rat and human Kp
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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.