Intestinal Absorption of HMG-CoA Reductase Inhibitor Pravastatin Mediated by Organic Anion Transporting Polypeptide
Purpose The purpose of this study is to clarify the impact of organic anion transporting polypeptide (Oatp) on intestinal absorption of the HMG-CoA reductase inhibitor, pravastatin. Methods OATP/Oatp-mediated pravastatin uptake was evaluated with Xenopus oocytes systems. Intestinal permeability was...
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| Veröffentlicht in: | Pharmaceutical research 2010-10, Vol.27 (10), p.2141-2149 |
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| creator | Shirasaka, Yoshiyuki Suzuki, Kensuke Nakanishi, Takeo Tamai, Ikumi |
| description | Purpose The purpose of this study is to clarify the impact of organic anion transporting polypeptide (Oatp) on intestinal absorption of the HMG-CoA reductase inhibitor, pravastatin. Methods OATP/Oatp-mediated pravastatin uptake was evaluated with Xenopus oocytes systems. Intestinal permeability was measured by an in situ closed loop method in rats. In vivo pravastatin absorption was kinetically assessed by measuring plasma concentration after oral administration in rats. Results Uptake of pravastatin by Oatp1a5, Oatp2b1, OATP1A2, and OATP2B1 cRNA-injected Xenopus oocytes was significantly increased compared with that by water-injected oocytes. Naringin, a potent inhibitor of Oatps and Mdr1, decreased the Oatp1a5-mediated uptake of pravastatin with IC ₅₀ value of 30.4 μM. Rat intestinal permeability of pravastatin was significantly reduced in the presence of 1,000 μM naringin. Similar results were obtained in in vivo absorption studies in rats. Furthermore, no significant change in the permeability was observed in the presence of elacridar, a potent inhibitor of both Mdr1 and Bcrp, though the permeability was significantly decreased in the presence of both elacridar and naringin, suggesting that Mdr1 and Bcrp are not involved in intestinal absorption of pravastatin. Conclusion Oatp, but not by Mdr1 or Bcrp, contributes to the intestinal absorption of pravastatin in rats. |
| doi_str_mv | 10.1007/s11095-010-0216-5 |
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| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_751868187</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2142921901</sourcerecordid><originalsourceid>FETCH-LOGICAL-c490t-2854f35c5db3ea3f988022db0037e1884d94f801d7056e427b8183622ff8d5593</originalsourceid><addsrcrecordid>eNp9kE1v1DAQhi1ERZfCD-ACFhLHtDP-iJ3jagXtSq1alVbiZjmxvaTaxsHOIu2_x6ss9MbJh3nedzwPIR8QzhFAXWREaGQFCBUwrCv5iixQKl41IH68JgtQTFRaCTwlb3N-AgCNjXhDThnUutasXpC8Hiafp36wW7psc0zj1MeBxkCvbi6rVVzSe-923WSzp-vhZ9_2U0z0LtnfNk-25OiNd72dvKPtnt6mjR36ji6HQ8lDskMeYyrUht7F7X70pd35d-Qk2G3274_vGXn89vVhdVVd316uV8vrqhMNTBXTUgQuO-la7i0PjdbAmGsBuPKotXCNCBrQKZC1F0y1GjWvGQtBOykbfkY-z71jir925UrzFHepXJqNklgEoFYFwhnqUsw5-WDG1D_btDcI5mDZzJZNsWwOlo0smY_H4l377N2_xF-tBfhyBGzu7DYUEV2fXzjOtQAFhWMzl8to2Pj08sP_bf80h4KNxm5SKX78zgA5oG4Aas7_AFYmnT4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>751868187</pqid></control><display><type>article</type><title>Intestinal Absorption of HMG-CoA Reductase Inhibitor Pravastatin Mediated by Organic Anion Transporting Polypeptide</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Shirasaka, Yoshiyuki ; Suzuki, Kensuke ; Nakanishi, Takeo ; Tamai, Ikumi</creator><creatorcontrib>Shirasaka, Yoshiyuki ; Suzuki, Kensuke ; Nakanishi, Takeo ; Tamai, Ikumi</creatorcontrib><description>Purpose The purpose of this study is to clarify the impact of organic anion transporting polypeptide (Oatp) on intestinal absorption of the HMG-CoA reductase inhibitor, pravastatin. Methods OATP/Oatp-mediated pravastatin uptake was evaluated with Xenopus oocytes systems. Intestinal permeability was measured by an in situ closed loop method in rats. In vivo pravastatin absorption was kinetically assessed by measuring plasma concentration after oral administration in rats. Results Uptake of pravastatin by Oatp1a5, Oatp2b1, OATP1A2, and OATP2B1 cRNA-injected Xenopus oocytes was significantly increased compared with that by water-injected oocytes. Naringin, a potent inhibitor of Oatps and Mdr1, decreased the Oatp1a5-mediated uptake of pravastatin with IC ₅₀ value of 30.4 μM. Rat intestinal permeability of pravastatin was significantly reduced in the presence of 1,000 μM naringin. Similar results were obtained in in vivo absorption studies in rats. Furthermore, no significant change in the permeability was observed in the presence of elacridar, a potent inhibitor of both Mdr1 and Bcrp, though the permeability was significantly decreased in the presence of both elacridar and naringin, suggesting that Mdr1 and Bcrp are not involved in intestinal absorption of pravastatin. Conclusion Oatp, but not by Mdr1 or Bcrp, contributes to the intestinal absorption of pravastatin in rats.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-010-0216-5</identifier><identifier>PMID: 20686826</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>Boston: Boston : Springer US</publisher><subject>Animals ; Biochemistry ; Biological and medical sciences ; Biological Transport ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Chromatography, Liquid ; Flavanones - pharmacology ; General pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology ; Ileum - metabolism ; In Vitro Techniques ; Intestinal Absorption ; Male ; Mdr1 ; Medical Law ; Medical sciences ; Membranes ; Multidrug Resistance-Associated Proteins - antagonists & inhibitors ; Multidrug Resistance-Associated Proteins - physiology ; naringin ; Oatp ; Oocytes - metabolism ; Organic Anion Transporters - antagonists & inhibitors ; Organic Anion Transporters - genetics ; Organic Anion Transporters - physiology ; Permeability ; Pharmaceutical sciences ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Pharmacy ; Polypeptides ; pravastatin ; Pravastatin - pharmacokinetics ; Pravastatin - pharmacology ; Rats ; Rats, Wistar ; Research Paper ; Rodents ; Small intestine ; Statins ; Tandem Mass Spectrometry ; Xenopus laevis</subject><ispartof>Pharmaceutical research, 2010-10, Vol.27 (10), p.2141-2149</ispartof><rights>Springer Science+Business Media, LLC 2010</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-2854f35c5db3ea3f988022db0037e1884d94f801d7056e427b8183622ff8d5593</citedby><cites>FETCH-LOGICAL-c490t-2854f35c5db3ea3f988022db0037e1884d94f801d7056e427b8183622ff8d5593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11095-010-0216-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11095-010-0216-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27926,27927,41490,42559,51321</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23384070$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20686826$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shirasaka, Yoshiyuki</creatorcontrib><creatorcontrib>Suzuki, Kensuke</creatorcontrib><creatorcontrib>Nakanishi, Takeo</creatorcontrib><creatorcontrib>Tamai, Ikumi</creatorcontrib><title>Intestinal Absorption of HMG-CoA Reductase Inhibitor Pravastatin Mediated by Organic Anion Transporting Polypeptide</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>Purpose The purpose of this study is to clarify the impact of organic anion transporting polypeptide (Oatp) on intestinal absorption of the HMG-CoA reductase inhibitor, pravastatin. Methods OATP/Oatp-mediated pravastatin uptake was evaluated with Xenopus oocytes systems. Intestinal permeability was measured by an in situ closed loop method in rats. In vivo pravastatin absorption was kinetically assessed by measuring plasma concentration after oral administration in rats. Results Uptake of pravastatin by Oatp1a5, Oatp2b1, OATP1A2, and OATP2B1 cRNA-injected Xenopus oocytes was significantly increased compared with that by water-injected oocytes. Naringin, a potent inhibitor of Oatps and Mdr1, decreased the Oatp1a5-mediated uptake of pravastatin with IC ₅₀ value of 30.4 μM. Rat intestinal permeability of pravastatin was significantly reduced in the presence of 1,000 μM naringin. Similar results were obtained in in vivo absorption studies in rats. Furthermore, no significant change in the permeability was observed in the presence of elacridar, a potent inhibitor of both Mdr1 and Bcrp, though the permeability was significantly decreased in the presence of both elacridar and naringin, suggesting that Mdr1 and Bcrp are not involved in intestinal absorption of pravastatin. Conclusion Oatp, but not by Mdr1 or Bcrp, contributes to the intestinal absorption of pravastatin in rats.</description><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Biological Transport</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Chromatography, Liquid</subject><subject>Flavanones - pharmacology</subject><subject>General pharmacology</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</subject><subject>Ileum - metabolism</subject><subject>In Vitro Techniques</subject><subject>Intestinal Absorption</subject><subject>Male</subject><subject>Mdr1</subject><subject>Medical Law</subject><subject>Medical sciences</subject><subject>Membranes</subject><subject>Multidrug Resistance-Associated Proteins - antagonists & inhibitors</subject><subject>Multidrug Resistance-Associated Proteins - physiology</subject><subject>naringin</subject><subject>Oatp</subject><subject>Oocytes - metabolism</subject><subject>Organic Anion Transporters - antagonists & inhibitors</subject><subject>Organic Anion Transporters - genetics</subject><subject>Organic Anion Transporters - physiology</subject><subject>Permeability</subject><subject>Pharmaceutical sciences</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Polypeptides</subject><subject>pravastatin</subject><subject>Pravastatin - pharmacokinetics</subject><subject>Pravastatin - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Research Paper</subject><subject>Rodents</subject><subject>Small intestine</subject><subject>Statins</subject><subject>Tandem Mass Spectrometry</subject><subject>Xenopus laevis</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kE1v1DAQhi1ERZfCD-ACFhLHtDP-iJ3jagXtSq1alVbiZjmxvaTaxsHOIu2_x6ss9MbJh3nedzwPIR8QzhFAXWREaGQFCBUwrCv5iixQKl41IH68JgtQTFRaCTwlb3N-AgCNjXhDThnUutasXpC8Hiafp36wW7psc0zj1MeBxkCvbi6rVVzSe-923WSzp-vhZ9_2U0z0LtnfNk-25OiNd72dvKPtnt6mjR36ji6HQ8lDskMeYyrUht7F7X70pd35d-Qk2G3274_vGXn89vVhdVVd316uV8vrqhMNTBXTUgQuO-la7i0PjdbAmGsBuPKotXCNCBrQKZC1F0y1GjWvGQtBOykbfkY-z71jir925UrzFHepXJqNklgEoFYFwhnqUsw5-WDG1D_btDcI5mDZzJZNsWwOlo0smY_H4l377N2_xF-tBfhyBGzu7DYUEV2fXzjOtQAFhWMzl8to2Pj08sP_bf80h4KNxm5SKX78zgA5oG4Aas7_AFYmnT4</recordid><startdate>20101001</startdate><enddate>20101001</enddate><creator>Shirasaka, Yoshiyuki</creator><creator>Suzuki, Kensuke</creator><creator>Nakanishi, Takeo</creator><creator>Tamai, Ikumi</creator><general>Boston : Springer US</general><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>FBQ</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>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>PRINS</scope></search><sort><creationdate>20101001</creationdate><title>Intestinal Absorption of HMG-CoA Reductase Inhibitor Pravastatin Mediated by Organic Anion Transporting Polypeptide</title><author>Shirasaka, Yoshiyuki ; Suzuki, Kensuke ; Nakanishi, Takeo ; Tamai, Ikumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-2854f35c5db3ea3f988022db0037e1884d94f801d7056e427b8183622ff8d5593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Biological Transport</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>Chromatography, Liquid</topic><topic>Flavanones - pharmacology</topic><topic>General pharmacology</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</topic><topic>Ileum - metabolism</topic><topic>In Vitro Techniques</topic><topic>Intestinal Absorption</topic><topic>Male</topic><topic>Mdr1</topic><topic>Medical Law</topic><topic>Medical sciences</topic><topic>Membranes</topic><topic>Multidrug Resistance-Associated Proteins - antagonists & inhibitors</topic><topic>Multidrug Resistance-Associated Proteins - physiology</topic><topic>naringin</topic><topic>Oatp</topic><topic>Oocytes - metabolism</topic><topic>Organic Anion Transporters - antagonists & inhibitors</topic><topic>Organic Anion Transporters - genetics</topic><topic>Organic Anion Transporters - physiology</topic><topic>Permeability</topic><topic>Pharmaceutical sciences</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Polypeptides</topic><topic>pravastatin</topic><topic>Pravastatin - pharmacokinetics</topic><topic>Pravastatin - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Research Paper</topic><topic>Rodents</topic><topic>Small intestine</topic><topic>Statins</topic><topic>Tandem Mass Spectrometry</topic><topic>Xenopus laevis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shirasaka, Yoshiyuki</creatorcontrib><creatorcontrib>Suzuki, Kensuke</creatorcontrib><creatorcontrib>Nakanishi, Takeo</creatorcontrib><creatorcontrib>Tamai, Ikumi</creatorcontrib><collection>AGRIS</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>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>ProQuest Central China</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shirasaka, Yoshiyuki</au><au>Suzuki, Kensuke</au><au>Nakanishi, Takeo</au><au>Tamai, Ikumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intestinal Absorption of HMG-CoA Reductase Inhibitor Pravastatin Mediated by Organic Anion Transporting Polypeptide</atitle><jtitle>Pharmaceutical research</jtitle><stitle>Pharm Res</stitle><addtitle>Pharm Res</addtitle><date>2010-10-01</date><risdate>2010</risdate><volume>27</volume><issue>10</issue><spage>2141</spage><epage>2149</epage><pages>2141-2149</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Purpose The purpose of this study is to clarify the impact of organic anion transporting polypeptide (Oatp) on intestinal absorption of the HMG-CoA reductase inhibitor, pravastatin. Methods OATP/Oatp-mediated pravastatin uptake was evaluated with Xenopus oocytes systems. Intestinal permeability was measured by an in situ closed loop method in rats. In vivo pravastatin absorption was kinetically assessed by measuring plasma concentration after oral administration in rats. Results Uptake of pravastatin by Oatp1a5, Oatp2b1, OATP1A2, and OATP2B1 cRNA-injected Xenopus oocytes was significantly increased compared with that by water-injected oocytes. Naringin, a potent inhibitor of Oatps and Mdr1, decreased the Oatp1a5-mediated uptake of pravastatin with IC ₅₀ value of 30.4 μM. Rat intestinal permeability of pravastatin was significantly reduced in the presence of 1,000 μM naringin. Similar results were obtained in in vivo absorption studies in rats. Furthermore, no significant change in the permeability was observed in the presence of elacridar, a potent inhibitor of both Mdr1 and Bcrp, though the permeability was significantly decreased in the presence of both elacridar and naringin, suggesting that Mdr1 and Bcrp are not involved in intestinal absorption of pravastatin. Conclusion Oatp, but not by Mdr1 or Bcrp, contributes to the intestinal absorption of pravastatin in rats.</abstract><cop>Boston</cop><pub>Boston : Springer US</pub><pmid>20686826</pmid><doi>10.1007/s11095-010-0216-5</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Biochemistry Biological and medical sciences Biological Transport Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Chromatography, Liquid Flavanones - pharmacology General pharmacology Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Ileum - metabolism In Vitro Techniques Intestinal Absorption Male Mdr1 Medical Law Medical sciences Membranes Multidrug Resistance-Associated Proteins - antagonists & inhibitors Multidrug Resistance-Associated Proteins - physiology naringin Oatp Oocytes - metabolism Organic Anion Transporters - antagonists & inhibitors Organic Anion Transporters - genetics Organic Anion Transporters - physiology Permeability Pharmaceutical sciences Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Pharmacology/Toxicology Pharmacy Polypeptides pravastatin Pravastatin - pharmacokinetics Pravastatin - pharmacology Rats Rats, Wistar Research Paper Rodents Small intestine Statins Tandem Mass Spectrometry Xenopus laevis |
| title | Intestinal Absorption of HMG-CoA Reductase Inhibitor Pravastatin Mediated by Organic Anion Transporting Polypeptide |
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