| Lipophilicity and transporter influence on blood-retinal barrier permeability: a comparison with blood-brain barrier permeability. | |
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MedLine Citation:
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PMID: 20859661 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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, [(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. 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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Authors:
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Ken-ichi Hosoya; Atsushi Yamamoto; Shin-ichi Akanuma; Masanori Tachikawa |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-22 |
Journal Detail:
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Title: Pharmaceutical research Volume: 27 ISSN: 1573-904X ISO Abbreviation: Pharm. Res. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: United States |
Other Details:
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Languages: eng Pagination: 2715-24 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. hosoyak@pha.u-toyama.ac.jp |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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