Transport of peptidomimetic thrombin inhibitors with a 3-amidino-phenylalanine structure : Permeability and efflux mechanism in monolayers of a human intestinal cell line (Caco-2)
Peptidomimetic thrombin inhibitors derived from Nalpha-(2-naphthylsulfonyl)-3-amidino-phenylalanine with different basic and acidic substituents were investigated with respect to their intestinal transport behavior. Intestinal permeability coefficients were studied using Caco-2 monolayers and a reve...
Gespeichert in:
| Veröffentlicht in: | Pharmaceutical research 2001-08, Vol.18 (8), p.1110-1118 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1118 |
|---|---|
| container_issue | 8 |
| container_start_page | 1110 |
| container_title | Pharmaceutical research |
| container_volume | 18 |
| creator | KAMM, Walter HAUPTMANN, Jörg BEHRENS, Isabel STÜRZEBECHER, Jörg DULLWEBER, Frank GOHLKE, Holger STUBBS, Milton KLEBE, Gerhard KISSEL, Thomas |
| description | Peptidomimetic thrombin inhibitors derived from Nalpha-(2-naphthylsulfonyl)-3-amidino-phenylalanine with different basic and acidic substituents were investigated with respect to their intestinal transport behavior.
Intestinal permeability coefficients were studied using Caco-2 monolayers and a reversed-phase HPLC method for quantitation.
Apparent permeability coefficients Papp of compounds with a free amidino group were in general low ( piperidine carboxylic acid methylester (ER 6-11) > piperidine carboxylic acids (ER 1.9-2.9) > piperazide (ER -0.17). Efflux of (1) was temperature-dependent, but independent of the enantiomeric configuration, accompanied by an increase in transepithelial electrical resistance (TEER), and could be reduced by P-gp inhibitors (PSC 833, Cremophor EL) but not by indomethacin. Replacement of the amidine group of (1) by aminomethyl-, amino-, and oxamidine- moieties drastically increased absorptive permeability (46-68 fold) with ER < 3.4. In contrast, the oxamidine with a C-terminal nipecotic acid residue (8) displayed also a temperature dependent efflux- without altering TEER (ER 22). This efflux was sensitive to PSC833/Cremophor EL and indomethacin.
Basic and acidic residues of amidino-phenylalanine-derived thrombin inhibitors mediate affinity to intestinal efflux pumps. presumably P-gp and MRP. P-gp mediated efflux was related to a net positive charge and accompanied by an increased TEER. Among the methylpiperide (1) promoieties studied the oxamidino group seems to be very promising in overcoming both transport and efflux problems frequently encountered with peptidomimetics containing amidines. |
| doi_str_mv | 10.1023/A:1010966708181 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_71226078</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>404179511</sourcerecordid><originalsourceid>FETCH-LOGICAL-c334t-99d8bfaae2d0a62eb5acdde1f0e1e082be4bbb3ba1081f7268f69826e7b8ecd3</originalsourceid><addsrcrecordid>eNpd0cuKFDEUBuAgitMzunYnQUR0UZpLXWc3NOMFBnTRC3fFSeoUlSGXMknh9HP5gqaxBXF1IHz8-TmHkBecvedMyA8315xxNrRtx3re80dkx5tOVgOrvz8mO9aJuuq7ml-Qy5TuGStoqJ-SC86b8tzzHfl1iODTGmKmYaYrrtlMwRmH2WialxicMp4avxhlcoiJ_jR5oUBlBc5MxodqXdAfLVjwxiNNOW46bxHpNf2G0SEoY00-UvATxXm22wN1qJeikyu51AUfLByxRJcCQJfNwenDjCkbD5ZqtJbaU_bbPehQiXfPyJMZbMLn53lFDh9vD_vP1d3XT1_2N3eVlrLO1TBMvZoBUEwMWoGqAT1NyGeGHFkvFNZKKamAl7XMnWj7uR160WKnetSTvCJv_sSuMfzYSp3RmXRqAx7DlsaOC9Gyri_w1X_wPmyxdE-jKKSpu6Ep6OUZbcrhNK7ROIjH8e8pCnh9BpA02LncRZv0j5NtI1v5G3LDnEc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>222654795</pqid></control><display><type>article</type><title>Transport of peptidomimetic thrombin inhibitors with a 3-amidino-phenylalanine structure : Permeability and efflux mechanism in monolayers of a human intestinal cell line (Caco-2)</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>KAMM, Walter ; HAUPTMANN, Jörg ; BEHRENS, Isabel ; STÜRZEBECHER, Jörg ; DULLWEBER, Frank ; GOHLKE, Holger ; STUBBS, Milton ; KLEBE, Gerhard ; KISSEL, Thomas</creator><creatorcontrib>KAMM, Walter ; HAUPTMANN, Jörg ; BEHRENS, Isabel ; STÜRZEBECHER, Jörg ; DULLWEBER, Frank ; GOHLKE, Holger ; STUBBS, Milton ; KLEBE, Gerhard ; KISSEL, Thomas</creatorcontrib><description>Peptidomimetic thrombin inhibitors derived from Nalpha-(2-naphthylsulfonyl)-3-amidino-phenylalanine with different basic and acidic substituents were investigated with respect to their intestinal transport behavior.
Intestinal permeability coefficients were studied using Caco-2 monolayers and a reversed-phase HPLC method for quantitation.
Apparent permeability coefficients Papp of compounds with a free amidino group were in general low (<10 x 10(-8) cm/s) and independent of the structure of the amide part (C-terminus). Polarized efflux, however, was strongly affected by substituents in the amide moiety yielding the following efflux ratios (ER): methylpiperidide (1) (ER 45) > piperidine carboxylic acid methylester (ER 6-11) > piperidine carboxylic acids (ER 1.9-2.9) > piperazide (ER -0.17). Efflux of (1) was temperature-dependent, but independent of the enantiomeric configuration, accompanied by an increase in transepithelial electrical resistance (TEER), and could be reduced by P-gp inhibitors (PSC 833, Cremophor EL) but not by indomethacin. Replacement of the amidine group of (1) by aminomethyl-, amino-, and oxamidine- moieties drastically increased absorptive permeability (46-68 fold) with ER < 3.4. In contrast, the oxamidine with a C-terminal nipecotic acid residue (8) displayed also a temperature dependent efflux- without altering TEER (ER 22). This efflux was sensitive to PSC833/Cremophor EL and indomethacin.
Basic and acidic residues of amidino-phenylalanine-derived thrombin inhibitors mediate affinity to intestinal efflux pumps. presumably P-gp and MRP. P-gp mediated efflux was related to a net positive charge and accompanied by an increased TEER. Among the methylpiperide (1) promoieties studied the oxamidino group seems to be very promising in overcoming both transport and efflux problems frequently encountered with peptidomimetics containing amidines.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/A:1010966708181</identifier><identifier>PMID: 11587481</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Amidines - chemistry ; Amidines - metabolism ; Bioavailability ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Caco-2 Cells ; Cell culture ; Cell Membrane Permeability ; Cell physiology ; Chemical Phenomena ; Chemistry, Physical ; Chromatography, High Pressure Liquid ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Fundamental and applied biological sciences. Psychology ; Glucose ; Glycoproteins ; Hemostatics - antagonists & inhibitors ; Humans ; Indicators and Reagents ; Intestinal Absorption - drug effects ; Investigations ; Medical sciences ; Membrane and intracellular transports ; Metabolism ; Metabolites ; Molecular and cellular biology ; Molecular Mimicry ; Peptides ; Permeability ; Pharmacology. Drug treatments ; Phenylalanine - analogs & derivatives ; Phenylalanine - chemistry ; Phenylalanine - metabolism ; Solubility ; Spectrometry, Fluorescence ; Spectrophotometry, Ultraviolet ; Structure-Activity Relationship ; Temperature ; Thrombin - antagonists & inhibitors</subject><ispartof>Pharmaceutical research, 2001-08, Vol.18 (8), p.1110-1118</ispartof><rights>2001 INIST-CNRS</rights><rights>Copyright Kluwer Academic Publishers Aug 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c334t-99d8bfaae2d0a62eb5acdde1f0e1e082be4bbb3ba1081f7268f69826e7b8ecd3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1136536$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11587481$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KAMM, Walter</creatorcontrib><creatorcontrib>HAUPTMANN, Jörg</creatorcontrib><creatorcontrib>BEHRENS, Isabel</creatorcontrib><creatorcontrib>STÜRZEBECHER, Jörg</creatorcontrib><creatorcontrib>DULLWEBER, Frank</creatorcontrib><creatorcontrib>GOHLKE, Holger</creatorcontrib><creatorcontrib>STUBBS, Milton</creatorcontrib><creatorcontrib>KLEBE, Gerhard</creatorcontrib><creatorcontrib>KISSEL, Thomas</creatorcontrib><title>Transport of peptidomimetic thrombin inhibitors with a 3-amidino-phenylalanine structure : Permeability and efflux mechanism in monolayers of a human intestinal cell line (Caco-2)</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>Peptidomimetic thrombin inhibitors derived from Nalpha-(2-naphthylsulfonyl)-3-amidino-phenylalanine with different basic and acidic substituents were investigated with respect to their intestinal transport behavior.
Intestinal permeability coefficients were studied using Caco-2 monolayers and a reversed-phase HPLC method for quantitation.
Apparent permeability coefficients Papp of compounds with a free amidino group were in general low (<10 x 10(-8) cm/s) and independent of the structure of the amide part (C-terminus). Polarized efflux, however, was strongly affected by substituents in the amide moiety yielding the following efflux ratios (ER): methylpiperidide (1) (ER 45) > piperidine carboxylic acid methylester (ER 6-11) > piperidine carboxylic acids (ER 1.9-2.9) > piperazide (ER -0.17). Efflux of (1) was temperature-dependent, but independent of the enantiomeric configuration, accompanied by an increase in transepithelial electrical resistance (TEER), and could be reduced by P-gp inhibitors (PSC 833, Cremophor EL) but not by indomethacin. Replacement of the amidine group of (1) by aminomethyl-, amino-, and oxamidine- moieties drastically increased absorptive permeability (46-68 fold) with ER < 3.4. In contrast, the oxamidine with a C-terminal nipecotic acid residue (8) displayed also a temperature dependent efflux- without altering TEER (ER 22). This efflux was sensitive to PSC833/Cremophor EL and indomethacin.
Basic and acidic residues of amidino-phenylalanine-derived thrombin inhibitors mediate affinity to intestinal efflux pumps. presumably P-gp and MRP. P-gp mediated efflux was related to a net positive charge and accompanied by an increased TEER. Among the methylpiperide (1) promoieties studied the oxamidino group seems to be very promising in overcoming both transport and efflux problems frequently encountered with peptidomimetics containing amidines.</description><subject>Amidines - chemistry</subject><subject>Amidines - metabolism</subject><subject>Bioavailability</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Caco-2 Cells</subject><subject>Cell culture</subject><subject>Cell Membrane Permeability</subject><subject>Cell physiology</subject><subject>Chemical Phenomena</subject><subject>Chemistry, Physical</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glucose</subject><subject>Glycoproteins</subject><subject>Hemostatics - antagonists & inhibitors</subject><subject>Humans</subject><subject>Indicators and Reagents</subject><subject>Intestinal Absorption - drug effects</subject><subject>Investigations</subject><subject>Medical sciences</subject><subject>Membrane and intracellular transports</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Molecular and cellular biology</subject><subject>Molecular Mimicry</subject><subject>Peptides</subject><subject>Permeability</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenylalanine - analogs & derivatives</subject><subject>Phenylalanine - chemistry</subject><subject>Phenylalanine - metabolism</subject><subject>Solubility</subject><subject>Spectrometry, Fluorescence</subject><subject>Spectrophotometry, Ultraviolet</subject><subject>Structure-Activity Relationship</subject><subject>Temperature</subject><subject>Thrombin - antagonists & inhibitors</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpd0cuKFDEUBuAgitMzunYnQUR0UZpLXWc3NOMFBnTRC3fFSeoUlSGXMknh9HP5gqaxBXF1IHz8-TmHkBecvedMyA8315xxNrRtx3re80dkx5tOVgOrvz8mO9aJuuq7ml-Qy5TuGStoqJ-SC86b8tzzHfl1iODTGmKmYaYrrtlMwRmH2WialxicMp4avxhlcoiJ_jR5oUBlBc5MxodqXdAfLVjwxiNNOW46bxHpNf2G0SEoY00-UvATxXm22wN1qJeikyu51AUfLByxRJcCQJfNwenDjCkbD5ZqtJbaU_bbPehQiXfPyJMZbMLn53lFDh9vD_vP1d3XT1_2N3eVlrLO1TBMvZoBUEwMWoGqAT1NyGeGHFkvFNZKKamAl7XMnWj7uR160WKnetSTvCJv_sSuMfzYSp3RmXRqAx7DlsaOC9Gyri_w1X_wPmyxdE-jKKSpu6Ep6OUZbcrhNK7ROIjH8e8pCnh9BpA02LncRZv0j5NtI1v5G3LDnEc</recordid><startdate>20010801</startdate><enddate>20010801</enddate><creator>KAMM, Walter</creator><creator>HAUPTMANN, Jörg</creator><creator>BEHRENS, Isabel</creator><creator>STÜRZEBECHER, Jörg</creator><creator>DULLWEBER, Frank</creator><creator>GOHLKE, Holger</creator><creator>STUBBS, Milton</creator><creator>KLEBE, Gerhard</creator><creator>KISSEL, Thomas</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20010801</creationdate><title>Transport of peptidomimetic thrombin inhibitors with a 3-amidino-phenylalanine structure : Permeability and efflux mechanism in monolayers of a human intestinal cell line (Caco-2)</title><author>KAMM, Walter ; HAUPTMANN, Jörg ; BEHRENS, Isabel ; STÜRZEBECHER, Jörg ; DULLWEBER, Frank ; GOHLKE, Holger ; STUBBS, Milton ; KLEBE, Gerhard ; KISSEL, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c334t-99d8bfaae2d0a62eb5acdde1f0e1e082be4bbb3ba1081f7268f69826e7b8ecd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amidines - chemistry</topic><topic>Amidines - metabolism</topic><topic>Bioavailability</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Caco-2 Cells</topic><topic>Cell culture</topic><topic>Cell Membrane Permeability</topic><topic>Cell physiology</topic><topic>Chemical Phenomena</topic><topic>Chemistry, Physical</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glucose</topic><topic>Glycoproteins</topic><topic>Hemostatics - antagonists & inhibitors</topic><topic>Humans</topic><topic>Indicators and Reagents</topic><topic>Intestinal Absorption - drug effects</topic><topic>Investigations</topic><topic>Medical sciences</topic><topic>Membrane and intracellular transports</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Molecular and cellular biology</topic><topic>Molecular Mimicry</topic><topic>Peptides</topic><topic>Permeability</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenylalanine - analogs & derivatives</topic><topic>Phenylalanine - chemistry</topic><topic>Phenylalanine - metabolism</topic><topic>Solubility</topic><topic>Spectrometry, Fluorescence</topic><topic>Spectrophotometry, Ultraviolet</topic><topic>Structure-Activity Relationship</topic><topic>Temperature</topic><topic>Thrombin - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KAMM, Walter</creatorcontrib><creatorcontrib>HAUPTMANN, Jörg</creatorcontrib><creatorcontrib>BEHRENS, Isabel</creatorcontrib><creatorcontrib>STÜRZEBECHER, Jörg</creatorcontrib><creatorcontrib>DULLWEBER, Frank</creatorcontrib><creatorcontrib>GOHLKE, Holger</creatorcontrib><creatorcontrib>STUBBS, Milton</creatorcontrib><creatorcontrib>KLEBE, Gerhard</creatorcontrib><creatorcontrib>KISSEL, Thomas</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KAMM, Walter</au><au>HAUPTMANN, Jörg</au><au>BEHRENS, Isabel</au><au>STÜRZEBECHER, Jörg</au><au>DULLWEBER, Frank</au><au>GOHLKE, Holger</au><au>STUBBS, Milton</au><au>KLEBE, Gerhard</au><au>KISSEL, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transport of peptidomimetic thrombin inhibitors with a 3-amidino-phenylalanine structure : Permeability and efflux mechanism in monolayers of a human intestinal cell line (Caco-2)</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2001-08-01</date><risdate>2001</risdate><volume>18</volume><issue>8</issue><spage>1110</spage><epage>1118</epage><pages>1110-1118</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Peptidomimetic thrombin inhibitors derived from Nalpha-(2-naphthylsulfonyl)-3-amidino-phenylalanine with different basic and acidic substituents were investigated with respect to their intestinal transport behavior.
Intestinal permeability coefficients were studied using Caco-2 monolayers and a reversed-phase HPLC method for quantitation.
Apparent permeability coefficients Papp of compounds with a free amidino group were in general low (<10 x 10(-8) cm/s) and independent of the structure of the amide part (C-terminus). Polarized efflux, however, was strongly affected by substituents in the amide moiety yielding the following efflux ratios (ER): methylpiperidide (1) (ER 45) > piperidine carboxylic acid methylester (ER 6-11) > piperidine carboxylic acids (ER 1.9-2.9) > piperazide (ER -0.17). Efflux of (1) was temperature-dependent, but independent of the enantiomeric configuration, accompanied by an increase in transepithelial electrical resistance (TEER), and could be reduced by P-gp inhibitors (PSC 833, Cremophor EL) but not by indomethacin. Replacement of the amidine group of (1) by aminomethyl-, amino-, and oxamidine- moieties drastically increased absorptive permeability (46-68 fold) with ER < 3.4. In contrast, the oxamidine with a C-terminal nipecotic acid residue (8) displayed also a temperature dependent efflux- without altering TEER (ER 22). This efflux was sensitive to PSC833/Cremophor EL and indomethacin.
Basic and acidic residues of amidino-phenylalanine-derived thrombin inhibitors mediate affinity to intestinal efflux pumps. presumably P-gp and MRP. P-gp mediated efflux was related to a net positive charge and accompanied by an increased TEER. Among the methylpiperide (1) promoieties studied the oxamidino group seems to be very promising in overcoming both transport and efflux problems frequently encountered with peptidomimetics containing amidines.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>11587481</pmid><doi>10.1023/A:1010966708181</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0724-8741 |
| ispartof | Pharmaceutical research, 2001-08, Vol.18 (8), p.1110-1118 |
| issn | 0724-8741 1573-904X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71226078 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Amidines - chemistry Amidines - metabolism Bioavailability Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Caco-2 Cells Cell culture Cell Membrane Permeability Cell physiology Chemical Phenomena Chemistry, Physical Chromatography, High Pressure Liquid Epithelial Cells - drug effects Epithelial Cells - metabolism Fundamental and applied biological sciences. Psychology Glucose Glycoproteins Hemostatics - antagonists & inhibitors Humans Indicators and Reagents Intestinal Absorption - drug effects Investigations Medical sciences Membrane and intracellular transports Metabolism Metabolites Molecular and cellular biology Molecular Mimicry Peptides Permeability Pharmacology. Drug treatments Phenylalanine - analogs & derivatives Phenylalanine - chemistry Phenylalanine - metabolism Solubility Spectrometry, Fluorescence Spectrophotometry, Ultraviolet Structure-Activity Relationship Temperature Thrombin - antagonists & inhibitors |
| title | Transport of peptidomimetic thrombin inhibitors with a 3-amidino-phenylalanine structure : Permeability and efflux mechanism in monolayers of a human intestinal cell line (Caco-2) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T10%3A36%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Transport%20of%20peptidomimetic%20thrombin%20inhibitors%20with%20a%203-amidino-phenylalanine%20structure%20:%20Permeability%20and%20efflux%20mechanism%20in%20monolayers%20of%20a%20human%20intestinal%20cell%20line%20(Caco-2)&rft.jtitle=Pharmaceutical%20research&rft.au=KAMM,%20Walter&rft.date=2001-08-01&rft.volume=18&rft.issue=8&rft.spage=1110&rft.epage=1118&rft.pages=1110-1118&rft.issn=0724-8741&rft.eissn=1573-904X&rft.coden=PHREEB&rft_id=info:doi/10.1023/A:1010966708181&rft_dat=%3Cproquest_pubme%3E404179511%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222654795&rft_id=info:pmid/11587481&rfr_iscdi=true |