In Silico Predictions of Blood-Brain Barrier Penetration: Considerations to “Keep in Mind”

2005 ◽  
Vol 315 (2) ◽  
pp. 477-483 ◽  
Author(s):  
Jay T. Goodwin ◽  
David E. Clark
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Brain Barrier ◽  
Blood Brain ◽  
Barrier Penetration ◽  
In Silico Predictions

A Bayesian Approach to in Silico Blood-Brain Barrier Penetration Modeling

2012 ◽  
Vol 52 (6) ◽  
pp. 1686-1697 ◽  
Author(s):  
Ines Filipa Martins ◽  
Ana L. Teixeira ◽  
Luis Pinheiro ◽  
Andre O. Falcao
Keyword(s):  
Blood Brain Barrier ◽  
Bayesian Approach ◽  
In Silico ◽  
Brain Barrier ◽  
Blood Brain ◽  
Barrier Penetration

Ligand and Structure-based Modeling of Passive Diffusion through the Blood-Brain Barrier

2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Passive Diffusion ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Different Types ◽  
The Brain

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.

scholarly journals Association Between Vancomycin Blood Brain Barrier Penetration and Clinical Response in Postsurgical Meningitis

2017 ◽  
Vol 20 ◽  
pp. 161 ◽  
Author(s):  
Qing Wang ◽  
Si Chen ◽  
Yan-Gang Zhou ◽  
Ping Xu ◽  
Yi-Ping Liu ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Response ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Serum Samples ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
Blood Brain ◽  
Barrier Penetration ◽  
White Blood Cell Counts

PURPOSE: This study investigated the association between vancomycin blood brain barrier penetration and clinical response in patients with postsurgical meningitis. METHODS: Adult patients with postsurgical meningitis were recruited. Eligible patients received vancomycin 500 mg every 6 h for at least 5 days. On day 3 or 4, cerebrospinal fluid (CSF) and simultaneous serum samples were obtained to determine CSF minimum concentrations (Cmin), serum Cmin and CSF to serum Cmin ratio. RESULTS: Twenty-two patients (14 men and 8 women; mean age of 52.6± 12.1 years) were recruited. The vancomycin Cmin was 3.63 ± 1.64 mg/L in CSF and 13.38 ± 5.36 mg/L in serum, with the CSF to serum Cmin ratio of 0.291 ± 0.118. The Cmin in serum and in CSF showed a significant correlation (p=0.005, r =0.575). The vancomycin CSF Cmin had a significant correlation with the decline of white blood cell counts (WBCs) in CSF (p=0.003, r =0.609). CSF Cmin, serum Cmin and CSF to serum Cmin ratio all showed no significant correlation with clinical response (p=0.335, 0.100, 0.679, respectively). CONCLUSIONS: There was a positive correlation between serum Cmin and CSF Cmin. However, only CSF Cmin is positively correlated with WBCs improvement in CSF. All other parameters such as serum Cmin, CSF Cmin and CSF to serum Cmin ratio had no correlation with clinical response. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals A TfR-Binding Cystine-Dense Peptide Promotes Blood–Brain Barrier Penetration of Bioactive Molecules

2020 ◽  
Vol 432 (14) ◽  
pp. 3989-4009 ◽  
Author(s):  
Zachary R. Crook ◽  
Emily Girard ◽  
Gregory P. Sevilla ◽  
Morgan Merrill ◽  
Della Friend ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Bioactive Molecules ◽  
Brain Barrier ◽  
Blood Brain ◽  
Barrier Penetration

Automatic QSAR modeling of ADME properties: blood–brain barrier penetration and aqueous solubility

2008 ◽  
Vol 22 (6-7) ◽  
pp. 431-440 ◽  
Author(s):  
Olga Obrezanova ◽  
Joelle M. R. Gola ◽  
Edmund J. Champness ◽  
Matthew D. Segall
Keyword(s):  
Blood Brain Barrier ◽  
Aqueous Solubility ◽  
Brain Barrier ◽  
Qsar Modeling ◽  
Blood Brain ◽  
Barrier Penetration ◽  
Adme Properties
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