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Lipophilicity and Transporter Influence on Blood-Retinal Barrier Permeability: A Comparison with Blood-Brain Barrier Permeability

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ABSTRACT

Purpose

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).

Methods

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.

Results

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 × exp (0.515 × 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, [3H]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.

Conclusions

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.

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ACKNOWLEDGEMENTS

The authors thank Dr. M. Tomi, Mr. M. Okamoto, and Miss Y. Ohkura for technical assistance. This study was supported, in part, by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS).

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Authors and Affiliations

  1. Department of Pharmaceutics Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Ken-ichi Hosoya, Atsushi Yamamoto, Shin-ichi Akanuma & Masanori Tachikawa

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  1. Ken-ichi Hosoya
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  2. Atsushi Yamamoto
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Correspondence to Ken-ichi Hosoya.

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Hosoya, Ki., Yamamoto, A., Akanuma, Si. et al. Lipophilicity and Transporter Influence on Blood-Retinal Barrier Permeability: A Comparison with Blood-Brain Barrier Permeability. Pharm Res 27, 2715–2724 (2010). https://doi.org/10.1007/s11095-010-0272-x

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