SK&F 97426-A: A Novel Bile Acid Sequestrant with Higher Affinities and Slower Dissociation Rates for Bile Acids in vitro Than Cholestyramine
SK&F 97426-A is a novel bile acid sequestrant that is threefold more potent than cholestyramine at increasing bile acid excretion in the hamster. SK&F 97426-A is a quaternary alkylammonium polymethacrylate that was selected for comparison with cholestyramine in vivo because of its superior i...
Gespeichert in:
| Veröffentlicht in: | Journal of pharmaceutical sciences 1997-01, Vol.86 (1), p.76-81 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 81 |
|---|---|
| container_issue | 1 |
| container_start_page | 76 |
| container_title | Journal of pharmaceutical sciences |
| container_volume | 86 |
| creator | Benson, G. Martin Alston, David R. Hickey, Deirdre M.B. Jaxa-Chamiec, Albert A. Whittaker, Caroline M. Haynes, Claire Glen, Alison Blanchard, Stephen Cresswell, Susan R. Suckling, Keith E. |
| description | SK&F 97426-A is a novel bile acid sequestrant that is threefold more potent than cholestyramine at increasing bile acid excretion in the hamster. SK&F 97426-A is a quaternary alkylammonium polymethacrylate that was selected for comparison with cholestyramine in vivo because of its superior in vitro bile acid binding properties. Association, dissociation, affinity, and capacity experiments were performed under physiologically relevant conditions with the most abundant bile acids found in human bile. The bile acids came to equilibrium with SK&F 97426-A and cholestyramine within ∼30min and 6 min, respectively. SK&F 97426-A and cholestyramine had similar capacities for all the bile acids (between 2.5 and 4mmol/g) and both had similar, very high affinities and slow dissociation rates for the dihydroxy bile acids. However, SK&F 97426-A had much higher affinities for the trihydroxy bile acids glycocholic acid and taurocholic acid than did cholestyramine. Dissociation of glycocholic acid and taurocholic acid from SK&F 97426-A was also much slower (27 and 25%, respectively, dissociated after 60 min) than from cholestyramine (89 and 84%, respectively, dissociated after 60 min). The higher affinities and slower dissociation rates of the trihydroxy bile acids for and from SK&F 97426-A probably account for the increased potency of SK&F 97426-A over cholestyramine in vivo. |
| doi_str_mv | 10.1021/js960207j |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_78797181</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0022354915502165</els_id><sourcerecordid>78797181</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4282-815e83094f187ea264ecdd4748899860e79e788542f4859423348a74c99f62e83</originalsourceid><addsrcrecordid>eNp1kMFuEzEQhlcIVELhwAMg-YAqIbFge71ru7eQkpaSFEQKHC3jnSUTNuvW3iTkHXhoXBKFC5ws-f_mH82XZU8ZfcUoZ68XUVeUU7m4lw1YyWleUSbvZwNKOc-LUuiH2aMYF5TSipblUXakUyKqYpD9mr0_GRMtBa_y4SkZkiu_hpa8wRbI0GFNZnC7gtgH2_Vkg_2cXOD3OQQybBrssEeIxHYJa_0m_Z5hjN6h7dF35JPtU9r48LcuEuzIGvvgyfXcdmQ0921q3wa7xA4eZw8a20Z4sn-Ps8_jt9eji3zy4fzdaDjJneCK54qVoAqqRcOUBMsrAa6uhRRKaa0qClKDVKoUvBGq1IIXhVBWCqd1U_E0epyd7Hpvgv9znVlidNC2tgO_ikYqqSVTLIEvdqALPsYAjbkJuLRhaxg1d-bNwXxin-1LV9-WUB_IveqUP9_nNjrbNsmow3jAeFmljWXCXu6wTXK2_f8-c_lxxnjC8x2OsYefB9yGH6aShSzN16tzM55O9eVk-sXcXVTseEh-1wjBRIfQOagxgOtN7fEft_0GnRy26w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>78797181</pqid></control><display><type>article</type><title>SK&F 97426-A: A Novel Bile Acid Sequestrant with Higher Affinities and Slower Dissociation Rates for Bile Acids in vitro Than Cholestyramine</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Alma/SFX Local Collection</source><creator>Benson, G. Martin ; Alston, David R. ; Hickey, Deirdre M.B. ; Jaxa-Chamiec, Albert A. ; Whittaker, Caroline M. ; Haynes, Claire ; Glen, Alison ; Blanchard, Stephen ; Cresswell, Susan R. ; Suckling, Keith E.</creator><creatorcontrib>Benson, G. Martin ; Alston, David R. ; Hickey, Deirdre M.B. ; Jaxa-Chamiec, Albert A. ; Whittaker, Caroline M. ; Haynes, Claire ; Glen, Alison ; Blanchard, Stephen ; Cresswell, Susan R. ; Suckling, Keith E.</creatorcontrib><description><![CDATA[SK&F 97426-A is a novel bile acid sequestrant that is threefold more potent than cholestyramine at increasing bile acid excretion in the hamster. SK&F 97426-A is a quaternary alkylammonium polymethacrylate that was selected for comparison with cholestyramine in vivo because of its superior in vitro bile acid binding properties. Association, dissociation, affinity, and capacity experiments were performed under physiologically relevant conditions with the most abundant bile acids found in human bile. The bile acids came to equilibrium with SK&F 97426-A and cholestyramine within ∼30min and 6 min, respectively. SK&F 97426-A and cholestyramine had similar capacities for all the bile acids (between 2.5 and 4mmol/g) and both had similar, very high affinities and slow dissociation rates for the dihydroxy bile acids. However, SK&F 97426-A had much higher affinities for the trihydroxy bile acids glycocholic acid and taurocholic acid than did cholestyramine. Dissociation of glycocholic acid and taurocholic acid from SK&F 97426-A was also much slower (27 and 25%, respectively, dissociated after 60 min) than from cholestyramine (89 and 84%, respectively, dissociated after 60 min). The higher affinities and slower dissociation rates of the trihydroxy bile acids for and from SK&F 97426-A probably account for the increased potency of SK&F 97426-A over cholestyramine in vivo.]]></description><identifier>ISSN: 0022-3549</identifier><identifier>EISSN: 1520-6017</identifier><identifier>DOI: 10.1021/js960207j</identifier><identifier>PMID: 9002463</identifier><identifier>CODEN: JPMSAE</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>Animals ; Anticholesteremic Agents - metabolism ; Anticholesteremic Agents - pharmacokinetics ; Bile Acids and Salts - metabolism ; Biological and medical sciences ; Cholestyramine Resin - metabolism ; Cholestyramine Resin - pharmacokinetics ; Cricetinae ; General and cellular metabolism. Vitamins ; Humans ; Medical sciences ; Pharmacology. Drug treatments ; Polymethacrylic Acids - metabolism ; Polymethacrylic Acids - pharmacokinetics</subject><ispartof>Journal of pharmaceutical sciences, 1997-01, Vol.86 (1), p.76-81</ispartof><rights>1997 Wiley-Liss, Inc., A Wiley Company</rights><rights>Copyright © 1997 Wiley‐Liss, Inc. and the American Pharmaceutical Association</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4282-815e83094f187ea264ecdd4748899860e79e788542f4859423348a74c99f62e83</citedby><cites>FETCH-LOGICAL-c4282-815e83094f187ea264ecdd4748899860e79e788542f4859423348a74c99f62e83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1021%2Fjs960207j$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1021%2Fjs960207j$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,4010,27900,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2561815$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9002463$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Benson, G. Martin</creatorcontrib><creatorcontrib>Alston, David R.</creatorcontrib><creatorcontrib>Hickey, Deirdre M.B.</creatorcontrib><creatorcontrib>Jaxa-Chamiec, Albert A.</creatorcontrib><creatorcontrib>Whittaker, Caroline M.</creatorcontrib><creatorcontrib>Haynes, Claire</creatorcontrib><creatorcontrib>Glen, Alison</creatorcontrib><creatorcontrib>Blanchard, Stephen</creatorcontrib><creatorcontrib>Cresswell, Susan R.</creatorcontrib><creatorcontrib>Suckling, Keith E.</creatorcontrib><title>SK&F 97426-A: A Novel Bile Acid Sequestrant with Higher Affinities and Slower Dissociation Rates for Bile Acids in vitro Than Cholestyramine</title><title>Journal of pharmaceutical sciences</title><addtitle>J. Pharm. Sci</addtitle><description><![CDATA[SK&F 97426-A is a novel bile acid sequestrant that is threefold more potent than cholestyramine at increasing bile acid excretion in the hamster. SK&F 97426-A is a quaternary alkylammonium polymethacrylate that was selected for comparison with cholestyramine in vivo because of its superior in vitro bile acid binding properties. Association, dissociation, affinity, and capacity experiments were performed under physiologically relevant conditions with the most abundant bile acids found in human bile. The bile acids came to equilibrium with SK&F 97426-A and cholestyramine within ∼30min and 6 min, respectively. SK&F 97426-A and cholestyramine had similar capacities for all the bile acids (between 2.5 and 4mmol/g) and both had similar, very high affinities and slow dissociation rates for the dihydroxy bile acids. However, SK&F 97426-A had much higher affinities for the trihydroxy bile acids glycocholic acid and taurocholic acid than did cholestyramine. Dissociation of glycocholic acid and taurocholic acid from SK&F 97426-A was also much slower (27 and 25%, respectively, dissociated after 60 min) than from cholestyramine (89 and 84%, respectively, dissociated after 60 min). The higher affinities and slower dissociation rates of the trihydroxy bile acids for and from SK&F 97426-A probably account for the increased potency of SK&F 97426-A over cholestyramine in vivo.]]></description><subject>Animals</subject><subject>Anticholesteremic Agents - metabolism</subject><subject>Anticholesteremic Agents - pharmacokinetics</subject><subject>Bile Acids and Salts - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cholestyramine Resin - metabolism</subject><subject>Cholestyramine Resin - pharmacokinetics</subject><subject>Cricetinae</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymethacrylic Acids - metabolism</subject><subject>Polymethacrylic Acids - pharmacokinetics</subject><issn>0022-3549</issn><issn>1520-6017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMFuEzEQhlcIVELhwAMg-YAqIbFge71ru7eQkpaSFEQKHC3jnSUTNuvW3iTkHXhoXBKFC5ws-f_mH82XZU8ZfcUoZ68XUVeUU7m4lw1YyWleUSbvZwNKOc-LUuiH2aMYF5TSipblUXakUyKqYpD9mr0_GRMtBa_y4SkZkiu_hpa8wRbI0GFNZnC7gtgH2_Vkg_2cXOD3OQQybBrssEeIxHYJa_0m_Z5hjN6h7dF35JPtU9r48LcuEuzIGvvgyfXcdmQ0921q3wa7xA4eZw8a20Z4sn-Ps8_jt9eji3zy4fzdaDjJneCK54qVoAqqRcOUBMsrAa6uhRRKaa0qClKDVKoUvBGq1IIXhVBWCqd1U_E0epyd7Hpvgv9znVlidNC2tgO_ikYqqSVTLIEvdqALPsYAjbkJuLRhaxg1d-bNwXxin-1LV9-WUB_IveqUP9_nNjrbNsmow3jAeFmljWXCXu6wTXK2_f8-c_lxxnjC8x2OsYefB9yGH6aShSzN16tzM55O9eVk-sXcXVTseEh-1wjBRIfQOagxgOtN7fEft_0GnRy26w</recordid><startdate>199701</startdate><enddate>199701</enddate><creator>Benson, G. Martin</creator><creator>Alston, David R.</creator><creator>Hickey, Deirdre M.B.</creator><creator>Jaxa-Chamiec, Albert A.</creator><creator>Whittaker, Caroline M.</creator><creator>Haynes, Claire</creator><creator>Glen, Alison</creator><creator>Blanchard, Stephen</creator><creator>Cresswell, Susan R.</creator><creator>Suckling, Keith E.</creator><general>Elsevier Inc</general><general>John Wiley & Sons, Inc</general><general>Wiley</general><general>American Pharmaceutical Association</general><scope>BSCLL</scope><scope>IQODW</scope><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>199701</creationdate><title>SK&F 97426-A: A Novel Bile Acid Sequestrant with Higher Affinities and Slower Dissociation Rates for Bile Acids in vitro Than Cholestyramine</title><author>Benson, G. Martin ; Alston, David R. ; Hickey, Deirdre M.B. ; Jaxa-Chamiec, Albert A. ; Whittaker, Caroline M. ; Haynes, Claire ; Glen, Alison ; Blanchard, Stephen ; Cresswell, Susan R. ; Suckling, Keith E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4282-815e83094f187ea264ecdd4748899860e79e788542f4859423348a74c99f62e83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Anticholesteremic Agents - metabolism</topic><topic>Anticholesteremic Agents - pharmacokinetics</topic><topic>Bile Acids and Salts - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cholestyramine Resin - metabolism</topic><topic>Cholestyramine Resin - pharmacokinetics</topic><topic>Cricetinae</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymethacrylic Acids - metabolism</topic><topic>Polymethacrylic Acids - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Benson, G. Martin</creatorcontrib><creatorcontrib>Alston, David R.</creatorcontrib><creatorcontrib>Hickey, Deirdre M.B.</creatorcontrib><creatorcontrib>Jaxa-Chamiec, Albert A.</creatorcontrib><creatorcontrib>Whittaker, Caroline M.</creatorcontrib><creatorcontrib>Haynes, Claire</creatorcontrib><creatorcontrib>Glen, Alison</creatorcontrib><creatorcontrib>Blanchard, Stephen</creatorcontrib><creatorcontrib>Cresswell, Susan R.</creatorcontrib><creatorcontrib>Suckling, Keith E.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><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>Journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Benson, G. Martin</au><au>Alston, David R.</au><au>Hickey, Deirdre M.B.</au><au>Jaxa-Chamiec, Albert A.</au><au>Whittaker, Caroline M.</au><au>Haynes, Claire</au><au>Glen, Alison</au><au>Blanchard, Stephen</au><au>Cresswell, Susan R.</au><au>Suckling, Keith E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SK&F 97426-A: A Novel Bile Acid Sequestrant with Higher Affinities and Slower Dissociation Rates for Bile Acids in vitro Than Cholestyramine</atitle><jtitle>Journal of pharmaceutical sciences</jtitle><addtitle>J. Pharm. Sci</addtitle><date>1997-01</date><risdate>1997</risdate><volume>86</volume><issue>1</issue><spage>76</spage><epage>81</epage><pages>76-81</pages><issn>0022-3549</issn><eissn>1520-6017</eissn><coden>JPMSAE</coden><abstract><![CDATA[SK&F 97426-A is a novel bile acid sequestrant that is threefold more potent than cholestyramine at increasing bile acid excretion in the hamster. SK&F 97426-A is a quaternary alkylammonium polymethacrylate that was selected for comparison with cholestyramine in vivo because of its superior in vitro bile acid binding properties. Association, dissociation, affinity, and capacity experiments were performed under physiologically relevant conditions with the most abundant bile acids found in human bile. The bile acids came to equilibrium with SK&F 97426-A and cholestyramine within ∼30min and 6 min, respectively. SK&F 97426-A and cholestyramine had similar capacities for all the bile acids (between 2.5 and 4mmol/g) and both had similar, very high affinities and slow dissociation rates for the dihydroxy bile acids. However, SK&F 97426-A had much higher affinities for the trihydroxy bile acids glycocholic acid and taurocholic acid than did cholestyramine. Dissociation of glycocholic acid and taurocholic acid from SK&F 97426-A was also much slower (27 and 25%, respectively, dissociated after 60 min) than from cholestyramine (89 and 84%, respectively, dissociated after 60 min). The higher affinities and slower dissociation rates of the trihydroxy bile acids for and from SK&F 97426-A probably account for the increased potency of SK&F 97426-A over cholestyramine in vivo.]]></abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>9002463</pmid><doi>10.1021/js960207j</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3549 |
| ispartof | Journal of pharmaceutical sciences, 1997-01, Vol.86 (1), p.76-81 |
| issn | 0022-3549 1520-6017 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_78797181 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | Animals Anticholesteremic Agents - metabolism Anticholesteremic Agents - pharmacokinetics Bile Acids and Salts - metabolism Biological and medical sciences Cholestyramine Resin - metabolism Cholestyramine Resin - pharmacokinetics Cricetinae General and cellular metabolism. Vitamins Humans Medical sciences Pharmacology. Drug treatments Polymethacrylic Acids - metabolism Polymethacrylic Acids - pharmacokinetics |
| title | SK&F 97426-A: A Novel Bile Acid Sequestrant with Higher Affinities and Slower Dissociation Rates for Bile Acids in vitro Than Cholestyramine |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T18%3A53%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=SK&F%2097426-A:%20A%20Novel%20Bile%20Acid%20Sequestrant%20with%20Higher%20Affinities%20and%20Slower%20Dissociation%20Rates%20for%20Bile%20Acids%20in%20vitro%20Than%20Cholestyramine&rft.jtitle=Journal%20of%20pharmaceutical%20sciences&rft.au=Benson,%20G.%20Martin&rft.date=1997-01&rft.volume=86&rft.issue=1&rft.spage=76&rft.epage=81&rft.pages=76-81&rft.issn=0022-3549&rft.eissn=1520-6017&rft.coden=JPMSAE&rft_id=info:doi/10.1021/js960207j&rft_dat=%3Cproquest_cross%3E78797181%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=78797181&rft_id=info:pmid/9002463&rft_els_id=S0022354915502165&rfr_iscdi=true |