Lipophilicity and Transporter Influence on Blood-Retinal Barrier Permeability: A Comparison with Blood-Brain Barrier Permeability
Lipophilicity and Transporter Influence on Blood-Retinal Barrier Permeability: A Comparison with Blood-Brain Barrier Permeability
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DOI：
10.1007/s11095-010-0272-x
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发表时间：
2010-12-01
影响因子：
3.7
通讯作者：
Tachikawa, Masanori
中科院分区：
文献类型：
--
作者：
Hosoya, Ken-ichi;Yamamoto, Atsushi;Tachikawa, Masanori
根据血-视网膜屏障（BRB）通透性与通透性之间的关系确定亲脂性趋势线，并与血-脑屏障（BBB）的亲脂性趋势线进行比较，测定了26种放射性标记化合物的视网膜（RUI）和脑摄取指数（BUI）。使用13种预期通过被动扩散从血液转运到视网膜的化合物和对数正辛醇/林格分布系数（DC）测定RUI。范围从-2.56至2.48。RUI值与DC的对数相关[RUI = 46.2 x exp（0.515 x log DC），r（2）= 0.807]。在BUI和亲脂性之间获得了类似的趋势。内流转运蛋白和P-糖蛋白（P-gp）底物的RUI值分别大于和小于亲脂性趋势线。与此相反，P-gp的底物[（3）H]维拉帕米的RUI值大于亲脂性趋势线，但BUI值不大于亲脂性趋势线，表明维拉帕米在BRB中存在内流转运系统，由RUI和DC值构建的亲脂性趋势线反映了药物在BRB中被动扩散的转运特性。
To determine the lipophilicity trend line from the relationship between the blood-retinal barrier (BRB) permeability and the lipophilicity of permeants and compare it with that of the blood-brain barrier (BBB).The retinal (RUI) and brain uptake index (BUI) of 26 radiolabeled compounds across the rat BRB and BBB, respectively, were measured using the carotid artery injection method.RUI was determined using 13 compounds expected to be transported from blood to the retina by passive diffusion and with a log n-octanol/Ringer distribution coefficient (DC) ranging from -2.56 to 2.48. The RUI values were correlated with the log of the DC [RUI = 46.2 x exp (0.515 x log DC), r (2) = 0.807]. A similar trend was obtained between BUI and lipophilicity. The RUI value for substrates of the influx transporters and P-glycoprotein (P-gp) was greater and smaller than the lipophilicity trend line, respectively. In contrast, [(3)H]verapamil, which is a substrate of P-gp, has a greater RUI value than the lipophilicity trend line, but not for BUI, suggesting that the BRB has an influx transport system for verapamil.The lipophilicity trend line constructed from the RUI and DC values is considered to reflect the transport properties of drugs undergoing passive diffusion across the BRB.