Permeability characteristics of primary cultured rabbit conjunctival epithelial cells to low molecular weight drugs
Purpose. To evaluate the permeability characteristics of primary cultured rabbit conjunctival epithelial cell (RCEC) layers to low molecular weight drugs of varying lipophilicity. Methods. 3H-mannitol; hydrophilic sotalol and atenolol; moderately lipophilic metoprolol, timolol, propranolol; and high...
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| Veröffentlicht in: | Current eye research 1996, Vol.15 (12), p.1170-1174 |
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| creator | Saha, Pratik Uchiyama, Tomomi Kim, Kwang-Jin Lee, Vincent H. L. |
| description | Purpose. To evaluate the permeability characteristics of primary cultured rabbit conjunctival epithelial cell (RCEC) layers to low molecular weight drugs of varying lipophilicity.
Methods. 3H-mannitol; hydrophilic sotalol and atenolol; moderately lipophilic metoprolol, timolol, propranolol; and highly lipophilic betaxolol were used as model compounds.
Results. The conjunctival apparent permeability coefficient (Papp) of mannitol (I × 10−7 cm/s) was 2.4 times lower than that of the most hydrophilic β-blocker, sotalol (Papp = 2.4 × 10 7 cm/s). Differences in the degree of tightness of the epithelial cell layers brought about a 30-fold difference in the transport of atenolol in favor of the leaky cell layers, while not affecting the transport of the lipophilic drug, propranolol. Within the log partition coefficient (PC) range of -0.62 (sotalol) and 3.44 (betaxolol), there was a hundred-fold difference in the Papp. A sigmoidal curve was used to depict the influence of lipophilicity on solute permeation across conjunctival epithelial cell layers. An effective half-maximal Papp was observed at a log PC value of 1.2.
Conclusions. These findings on the lipophilicity effect on drug transport are generally similar to those reported for the isolated rabbit conjunctiva, suggesting the utility of cultured rabbit conjunctival epithelial cell layers as an in vitro model for evaluating drug transport. |
| doi_str_mv | 10.3109/02713689608995152 |
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Methods. 3H-mannitol; hydrophilic sotalol and atenolol; moderately lipophilic metoprolol, timolol, propranolol; and highly lipophilic betaxolol were used as model compounds.
Results. The conjunctival apparent permeability coefficient (Papp) of mannitol (I × 10−7 cm/s) was 2.4 times lower than that of the most hydrophilic β-blocker, sotalol (Papp = 2.4 × 10 7 cm/s). Differences in the degree of tightness of the epithelial cell layers brought about a 30-fold difference in the transport of atenolol in favor of the leaky cell layers, while not affecting the transport of the lipophilic drug, propranolol. Within the log partition coefficient (PC) range of -0.62 (sotalol) and 3.44 (betaxolol), there was a hundred-fold difference in the Papp. A sigmoidal curve was used to depict the influence of lipophilicity on solute permeation across conjunctival epithelial cell layers. An effective half-maximal Papp was observed at a log PC value of 1.2.
Conclusions. These findings on the lipophilicity effect on drug transport are generally similar to those reported for the isolated rabbit conjunctiva, suggesting the utility of cultured rabbit conjunctival epithelial cell layers as an in vitro model for evaluating drug transport.</description><identifier>ISSN: 0271-3683</identifier><identifier>EISSN: 1460-2202</identifier><identifier>DOI: 10.3109/02713689608995152</identifier><identifier>PMID: 9018431</identifier><language>eng</language><publisher>England: Informa UK Ltd</publisher><subject>Adrenergic beta-Antagonists - pharmacokinetics ; Animals ; Biological Transport ; Cell Membrane Permeability - drug effects ; Cells, Cultured ; Conjunctiva - cytology ; Conjunctiva - metabolism ; Diuretics, Osmotic - pharmacokinetics ; Epithelial Cells ; Epithelium - metabolism ; lipophilicity ; low molecular weight drugs ; Mannitol - pharmacokinetics ; Molecular Weight ; permeability characteristics ; primary cultured rabbit conjunctival epithelial cells ; Rabbits ; Tight Junctions - physiology</subject><ispartof>Current eye research, 1996, Vol.15 (12), p.1170-1174</ispartof><rights>1996 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 1996</rights><rights>Copyright Swets & Zeitlinger bv Dec 1996</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-6e4b0a23d32839e3f13347a6069bec57dc87ff828af153ecba464099d6d4fb5a3</citedby><cites>FETCH-LOGICAL-c494t-6e4b0a23d32839e3f13347a6069bec57dc87ff828af153ecba464099d6d4fb5a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.3109/02713689608995152$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.3109/02713689608995152$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,776,780,4010,27900,27901,27902,59620,59726,60409,60515,61194,61229,61375,61410</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9018431$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saha, Pratik</creatorcontrib><creatorcontrib>Uchiyama, Tomomi</creatorcontrib><creatorcontrib>Kim, Kwang-Jin</creatorcontrib><creatorcontrib>Lee, Vincent H. L.</creatorcontrib><title>Permeability characteristics of primary cultured rabbit conjunctival epithelial cells to low molecular weight drugs</title><title>Current eye research</title><addtitle>Curr Eye Res</addtitle><description>Purpose. To evaluate the permeability characteristics of primary cultured rabbit conjunctival epithelial cell (RCEC) layers to low molecular weight drugs of varying lipophilicity.
Methods. 3H-mannitol; hydrophilic sotalol and atenolol; moderately lipophilic metoprolol, timolol, propranolol; and highly lipophilic betaxolol were used as model compounds.
Results. The conjunctival apparent permeability coefficient (Papp) of mannitol (I × 10−7 cm/s) was 2.4 times lower than that of the most hydrophilic β-blocker, sotalol (Papp = 2.4 × 10 7 cm/s). Differences in the degree of tightness of the epithelial cell layers brought about a 30-fold difference in the transport of atenolol in favor of the leaky cell layers, while not affecting the transport of the lipophilic drug, propranolol. Within the log partition coefficient (PC) range of -0.62 (sotalol) and 3.44 (betaxolol), there was a hundred-fold difference in the Papp. A sigmoidal curve was used to depict the influence of lipophilicity on solute permeation across conjunctival epithelial cell layers. An effective half-maximal Papp was observed at a log PC value of 1.2.
Conclusions. These findings on the lipophilicity effect on drug transport are generally similar to those reported for the isolated rabbit conjunctiva, suggesting the utility of cultured rabbit conjunctival epithelial cell layers as an in vitro model for evaluating drug transport.</description><subject>Adrenergic beta-Antagonists - pharmacokinetics</subject><subject>Animals</subject><subject>Biological Transport</subject><subject>Cell Membrane Permeability - drug effects</subject><subject>Cells, Cultured</subject><subject>Conjunctiva - cytology</subject><subject>Conjunctiva - metabolism</subject><subject>Diuretics, Osmotic - pharmacokinetics</subject><subject>Epithelial Cells</subject><subject>Epithelium - metabolism</subject><subject>lipophilicity</subject><subject>low molecular weight drugs</subject><subject>Mannitol - pharmacokinetics</subject><subject>Molecular Weight</subject><subject>permeability characteristics</subject><subject>primary cultured rabbit conjunctival epithelial cells</subject><subject>Rabbits</subject><subject>Tight Junctions - physiology</subject><issn>0271-3683</issn><issn>1460-2202</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc2L1TAUxYMo43P0D3AhBBfuqkmTpg26GQa_YEAXui636c00j7R5JqmP-e9NeQ_xg1kl5Jzf4eReQp5z9lpwpt-wuuVCdVqxTuuGN_UDsuNSsaquWf2Q7Da9KgbxmDxJac_Y9iAvyIVmvJOC70j6inFGGJx3-Y6aCSKYjNGl7EyiwdJDdDPEIq0-rxFHGmEYXKYmLPt1Mdn9BE_x4PKE3pWrQe8TzYH6cKRz8FhAiPSI7nbKdIzrbXpKHlnwCZ-dz0vy_cP7b9efqpsvHz9fX91URmqZK4VyYFCLUdSd0CgsF0K2oJjSA5qmHU3XWtvVHVjeCDQDSCWZ1qMapR0aEJfk1Sn3EMOPFVPuZ5e2frBgWFPfdkpzxXkxvvzHuA9rXEq3nuum5qWOKiZ-MpkYUopo-_Noes76bRv9f9sozItz8DrMOP4mzuMv-ruT7hYb4gzHEP3YZ7jzIdoIi3Fpi74__u1f-ITg82Qg4h8fuJf-BShrrIM</recordid><startdate>1996</startdate><enddate>1996</enddate><creator>Saha, Pratik</creator><creator>Uchiyama, Tomomi</creator><creator>Kim, Kwang-Jin</creator><creator>Lee, Vincent H. L.</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><general>Swets & Zeitlinger bv</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>1996</creationdate><title>Permeability characteristics of primary cultured rabbit conjunctival epithelial cells to low molecular weight drugs</title><author>Saha, Pratik ; Uchiyama, Tomomi ; Kim, Kwang-Jin ; Lee, Vincent H. L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-6e4b0a23d32839e3f13347a6069bec57dc87ff828af153ecba464099d6d4fb5a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Adrenergic beta-Antagonists - pharmacokinetics</topic><topic>Animals</topic><topic>Biological Transport</topic><topic>Cell Membrane Permeability - drug effects</topic><topic>Cells, Cultured</topic><topic>Conjunctiva - cytology</topic><topic>Conjunctiva - metabolism</topic><topic>Diuretics, Osmotic - pharmacokinetics</topic><topic>Epithelial Cells</topic><topic>Epithelium - metabolism</topic><topic>lipophilicity</topic><topic>low molecular weight drugs</topic><topic>Mannitol - pharmacokinetics</topic><topic>Molecular Weight</topic><topic>permeability characteristics</topic><topic>primary cultured rabbit conjunctival epithelial cells</topic><topic>Rabbits</topic><topic>Tight Junctions - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saha, Pratik</creatorcontrib><creatorcontrib>Uchiyama, Tomomi</creatorcontrib><creatorcontrib>Kim, Kwang-Jin</creatorcontrib><creatorcontrib>Lee, Vincent H. L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Current eye research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saha, Pratik</au><au>Uchiyama, Tomomi</au><au>Kim, Kwang-Jin</au><au>Lee, Vincent H. L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Permeability characteristics of primary cultured rabbit conjunctival epithelial cells to low molecular weight drugs</atitle><jtitle>Current eye research</jtitle><addtitle>Curr Eye Res</addtitle><date>1996</date><risdate>1996</risdate><volume>15</volume><issue>12</issue><spage>1170</spage><epage>1174</epage><pages>1170-1174</pages><issn>0271-3683</issn><eissn>1460-2202</eissn><abstract>Purpose. To evaluate the permeability characteristics of primary cultured rabbit conjunctival epithelial cell (RCEC) layers to low molecular weight drugs of varying lipophilicity.
Methods. 3H-mannitol; hydrophilic sotalol and atenolol; moderately lipophilic metoprolol, timolol, propranolol; and highly lipophilic betaxolol were used as model compounds.
Results. The conjunctival apparent permeability coefficient (Papp) of mannitol (I × 10−7 cm/s) was 2.4 times lower than that of the most hydrophilic β-blocker, sotalol (Papp = 2.4 × 10 7 cm/s). Differences in the degree of tightness of the epithelial cell layers brought about a 30-fold difference in the transport of atenolol in favor of the leaky cell layers, while not affecting the transport of the lipophilic drug, propranolol. Within the log partition coefficient (PC) range of -0.62 (sotalol) and 3.44 (betaxolol), there was a hundred-fold difference in the Papp. A sigmoidal curve was used to depict the influence of lipophilicity on solute permeation across conjunctival epithelial cell layers. An effective half-maximal Papp was observed at a log PC value of 1.2.
Conclusions. These findings on the lipophilicity effect on drug transport are generally similar to those reported for the isolated rabbit conjunctiva, suggesting the utility of cultured rabbit conjunctival epithelial cell layers as an in vitro model for evaluating drug transport.</abstract><cop>England</cop><pub>Informa UK Ltd</pub><pmid>9018431</pmid><doi>10.3109/02713689608995152</doi><tpages>5</tpages></addata></record> |
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| ispartof | Current eye research, 1996, Vol.15 (12), p.1170-1174 |
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| source | MEDLINE; Taylor & Francis Medical Library - CRKN; Taylor & Francis Journals Complete |
| subjects | Adrenergic beta-Antagonists - pharmacokinetics Animals Biological Transport Cell Membrane Permeability - drug effects Cells, Cultured Conjunctiva - cytology Conjunctiva - metabolism Diuretics, Osmotic - pharmacokinetics Epithelial Cells Epithelium - metabolism lipophilicity low molecular weight drugs Mannitol - pharmacokinetics Molecular Weight permeability characteristics primary cultured rabbit conjunctival epithelial cells Rabbits Tight Junctions - physiology |
| title | Permeability characteristics of primary cultured rabbit conjunctival epithelial cells to low molecular weight drugs |
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