Rapid screening of blood-brain barrier penetration of drugs using the immobilized artificial membrane phosphatidylcholine column chromatography

• Published in: Journal of biomolecular screening Vol. 11; no. 1; pp. 13 - 20
• Main Authors: Yoon, Chi Ho, Kim, Soo Jin, Shin, Beom Soo, Lee, Kang Choon, Yoo, Sun Dong
• Format: Journal Article
• Language: English
• Published: United States 01.02.2006
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; Animals; Biological Assay; Blood-Brain Barrier - metabolism; Central Nervous System; Chromatography - instrumentation; Chromatography - methods; Cyclic Nucleotide Phosphodiesterases, Type 4; Drug Evaluation, Preclinical - instrumentation; Drug Evaluation, Preclinical - methods; Humans; Membranes, Artificial; Permeability; Pharmaceutical Preparations - metabolism; Phosphatidylcholines - metabolism; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Statistics as Topic
• ISSN: 1087-0571; 2472-5552
• DOI: 10.1177/1087057105281656

The chromatographic capacity factors (kIAM) of 23 structurally diverse drugs were measured by the immobilized artificial membrane (IAM) phosphatidylcholine chromatography for the prediction of blood-brain barrier (BBB) penetration. The kIAM was determined using the mobile 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 prediction method 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.