Application of Membrane Permeability Evaluated in In Vitro Analyses to Estimate Blood-Retinal Barrier Permeability

作者：Kubo Yoshiyuki; Fukui Eri; Akanuma Shin Ichi; Tachikawa Masanori; Hosoya Ken Ichi^*

来源：Journal of Pharmaceutical Sciences, 2012, 101(7): 2596-2605.

DOI：10.1002/jps.23171

• retinal drug delivery
• permeability
• membrane transport
• passive diffusion/transport
• membrane transporter
• in vitro/in vivo correlations (IVIVC)

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 x 10 x exp (0.994 x log P-app), r(2) = 0.660] and a log of the V [RUI = 26.5 x exp (1.55 x 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 x exp (0.887 x 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.

• 出版日期2012-7