title: Rapid screening of blood-brain barrier penetration of drugs using the immobilized artificial membrane phosphatidylcholine column chromatography.
abstract: 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.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Gyeonggi-do, Korea.
authors.forename: Chi Ho
authors.initials: CH
authors.lastname: Yoon
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001681:Biological Assay; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002490:Central Nervous System; D002845:Chromatography / Q000295:instrumentation* / Q000379:methods*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D008567:Membranes, Artificial; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013223:Statistics as Topic
chemical_list: D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4