Faculty Opinions recommendation of Determination of in Vitro and in Silico Indexes for the Modeling of Blood-Brain Barrier Partitioning of Drugs via Micellar and Immobilized Artificial Membrane Liquid Chromatography.

2017 ◽  
Author(s):  
John Lowe
Keyword(s):  
Liquid Chromatography ◽  
Blood Brain Barrier ◽  
In Silico ◽  
Brain Barrier ◽  
Artificial Membrane ◽  
Immobilized Artificial Membrane ◽  
Blood Brain

scholarly journals Rapid Screening of Blood-Brain Barrier Penetration of Drugs Using the Immobilized Artificial Membrane Phosphatidylcholine Column Chromatography

2005 ◽  
Vol 11 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Chi Ho Yoon ◽  
Soo Jin Kim ◽  
Beom Soo Shin ◽  
Kang Choon Lee ◽  
Sun Dong Yoo
Keyword(s):  
Blood Brain Barrier ◽  
Prediction Method ◽  
Brain Barrier ◽  
Rapid Screening ◽  
Artificial Membrane ◽  
Immobilized Artificial Membrane ◽  
Blood Brain ◽  
Cns Penetration

The chromatographic capacity factors (kIAM) of 23 structurally diverse drugs were measured by the immobilized artificial membrane (kIAM) phosphatidylcholine chromatography for the prediction of blood-brain barrier (BBB) penetration. The kIAM was determined using themobile phase consisting of acetonitrile:DPBS (20:80 v/v) and corrected for the molar volume of the solutes (kIAM/MWn). The correlation between kIAM/MWn and CNS penetration was highest when measured at pH 5.5 with the power function of n = 4. This in vitro predictionmethod was validated with 7 newly synthesized PDE-4 inhibitors. The relationship between in vivo plasma-to-brain concentration ratios and in vitro CNS penetration was excellent ( r= 0.959). The developed in vitro prediction method may be used as a rapid screening tool for BBB penetration of drugs with passive transport mechanism, with high success, low cost, and reproducibility.

scholarly journals Neuropharmacokinetic visualization of regional and subregional unbound antipsychotic drug transport across the blood–brain barrier

2021 ◽  
Author(s):  
Dominika Luptáková ◽  
Theodosia Vallianatou ◽  
Anna Nilsson ◽  
Reza Shariatgorji ◽  
Margareta Hammarlund-Udenaes ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Drug Transport ◽  
Mass Spectrometry Imaging ◽  
Brain Regions ◽  
Brain Barrier ◽  
Blood Brain ◽  
Comprehensive Determination

AbstractComprehensive determination of the extent of drug transport across the region-specific blood–brain barrier (BBB) is a major challenge in preclinical studies. Multiple approaches are needed to determine the regional free (unbound) drug concentration at which a drug engages with its therapeutic target. We present an approach that merges in vivo and in vitro neuropharmacokinetic investigations with mass spectrometry imaging to quantify and visualize both the extent of unbound drug BBB transport and the post-BBB cerebral distribution of drugs at regional and subregional levels. Direct imaging of the antipsychotic drugs risperidone, clozapine, and olanzapine using this approach enabled differentiation of regional and subregional BBB transport characteristics at 20-µm resolution in small brain regions, which could not be achieved by other means. Our approach allows investigation of heterogeneity in BBB transport and presents new possibilities for molecular psychiatrists by facilitating interpretation of regional target-site exposure results and decision-making.

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