title: Application of membrane permeability evaluated in in vitro analyses to estimate blood-retinal barrier permeability.
abstract: The relationship between the in vitro membrane permeability and systemic blood-retinal barrier (BRB) permeability of drugs was investigated. To determine membrane permeability trend lines in this relationship, the apparent permeability (P(app)) and initial uptake rate (V) of 23 compounds were evaluated in a parallel artificial membrane permeability assay and the uptake study with a rat retinal endothelial cell line (TR-iBRB2 cells) for comparison with their retinal uptake index (RUI). The RUI values of compounds undergoing passive diffusion across the BRB were correlated with a log of the P(app) [RUI = 7.93 × 10 × exp (0.994 × log P(app)), r(2) = 0.660] and a log of the V [RUI = 26.5 × exp (1.55 × log V), r(2) = 0.581]. The RUI values of compounds undergoing carrier-mediated transport across the BRB were correlated with a log of the V [RUI = 26.5 × exp (0.887 × log V), r(2) = 0.559]. These results showed that the membrane permeability trend lines derived from the RUI and V values reflect the transport of drugs at the BRB, suggesting that an in vitro analysis-based estimation of the BRB permeability can be obtained using TR-iBRB2 cells and membrane permeability trend lines.
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kubo
authors.forename: Eri
authors.initials: E
authors.lastname: Fukui
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Akanuma
authors.forename: Masanori
authors.initials: M
authors.lastname: Tachikawa
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hosoya
mesh_terms: D000818:Animals; D001692:Biological Transport; D001813:Blood-Retinal Barrier / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability; D004058:Diffusion; D042783:Endothelial Cells / Q000378:metabolism; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010599:Pharmacokinetics; D051381:Rats; D012160:Retina / Q000166:cytology*
chemical_list: D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations