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

College of Pharmacy, Sungkyunkwan University, Gyeonggi-do, Korea

Soo Jin Kim

C&C Research Laboratories, Gyeonggi-do, Korea

Beom Soo Shin

Kang Choon Lee

College of Pharmacy, Sungkyunkwan University, Gyeonggi-do, Korea

Sun Dong Yoo

College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do, 440-746, Korea; sdyoo{at}skku.ac.kr

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.

Key Words: immobilized artificial membrane • blood-brain barrier • CNS penetration • high-throughput screening

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This version was published on February 1, 2006

Journal of Biomolecular Screening, Vol. 11, No. 1, 13-20 (2006)
DOI: 10.1177/1087057105281656


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Yoon, C. H. Articles by Yoo, S. D. Search for Related Content PubMed PubMed Citation Articles by Yoon, C. H. Articles by Yoo, S. D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LECITHIN Medline Plus Health Information Medicines Social Bookmarking                         What's this?