Rapid Screening of Blood-Brain Barrier Penetration of Drugs Using the Immobilized Artificial Membrane Phosphatidylcholine Column Chromatography
Open Access
- 1 February 2006
- journal article
- Published by Elsevier BV in SLAS Discovery
- Vol. 11 (1), 13-20
- https://doi.org/10.1177/1087057105281656
Abstract
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.Keywords
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