Comparative pharmacokinetics and bioavailability of escin Ia and isoescin Ia after administration of escin and of pure escin Ia and isoescin Ia in rat
A study was carried out to investigate the pharmacokinetic properties of escin Ia and isoescin Ia in rats and the pharmacokinetic differences between sodium escinate and pure escin Ia and isoescin Ia. Their bidirectional intercoversion in vivo has not been previously reported. Escin Ia and isoescin...
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| Veröffentlicht in: | Journal of ethnopharmacology 2012-01, Vol.139 (1), p.201-206 |
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| creator | Wu, Xiu-Jun Zhang, Meng-Liang Cui, Xiang-Yong Gao, Feng He, Qun Li, Xiao-Jiao Zhang, Ji-Wen Fawcett, J. Paul Gu, Jing-Kai |
| description | A study was carried out to investigate the pharmacokinetic properties of escin Ia and isoescin Ia in rats and the pharmacokinetic differences between sodium escinate and pure escin Ia and isoescin Ia. Their bidirectional intercoversion in vivo has not been previously reported.
Escin Ia and isoescin Ia have been traditionally used clinically as the chief active ingredients of escin, a major triterpene saponin isolated from horse chestnut (Aesculus hippocastanum) seeds for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema.
To establish a sensitive LC–MS/MS method and investigate the pharmacokinetic properties of escin Ia and isoescin Ia in rats and the pharmacokinetics difference of sodium escinate with pure escin Ia and isoescin Ia. The absolute bioavailability of escin Ia and isoescin Ia and the bidirectional interconversion of them in vivo were also scarcely reported.
Wister rats were administrated an intravenous (i.v.) dose (1.7mg/kg) of sodium escinate (corresponding to 0.5mg/kg of escin Ia and 0.5mg/kg of isoescin Ia, respectively) and an i.v. dose (0.5mg/kg) or oral dose (4mg/kg) of pure escin Ia or isoescin Ia, respectively. At different time points, the concentrations of escin Ia and isoescin Ia in rat plasma were determined by LC–MS/MS method. Main pharmacokinetic parameters including t1/2, MRT, CL, Vd, AUC and F were estimated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany) and statistical analysis was performed using the Student's t-test with P |
| doi_str_mv | 10.1016/j.jep.2011.11.003 |
| format | Article |
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Escin Ia and isoescin Ia have been traditionally used clinically as the chief active ingredients of escin, a major triterpene saponin isolated from horse chestnut (Aesculus hippocastanum) seeds for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema.
To establish a sensitive LC–MS/MS method and investigate the pharmacokinetic properties of escin Ia and isoescin Ia in rats and the pharmacokinetics difference of sodium escinate with pure escin Ia and isoescin Ia. The absolute bioavailability of escin Ia and isoescin Ia and the bidirectional interconversion of them in vivo were also scarcely reported.
Wister rats were administrated an intravenous (i.v.) dose (1.7mg/kg) of sodium escinate (corresponding to 0.5mg/kg of escin Ia and 0.5mg/kg of isoescin Ia, respectively) and an i.v. dose (0.5mg/kg) or oral dose (4mg/kg) of pure escin Ia or isoescin Ia, respectively. At different time points, the concentrations of escin Ia and isoescin Ia in rat plasma were determined by LC–MS/MS method. Main pharmacokinetic parameters including t1/2, MRT, CL, Vd, AUC and F were estimated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany) and statistical analysis was performed using the Student's t-test with P<0.05 as the level of significance.
After administration of sodium escinate, the t1/2 and MRT values for both escin Ia and isoescin Ia were larger than corresponding values for the compounds given alone. Absorption of escin Ia and isoescin Ia was very low with F values both <0.25%. Escin Ia and isoescin Ia were found to form the other isomer in vivo with the conversion of escin Ia to isoescin Ia being much extensive than from isoescin Ia to escin Ia.
Comparison of the pharmacokinetics of escin Ia and isoescin Ia given alone and together in rat suggest that administration of herbal preparations of escin for clinical use may provide longer duration of action than administration of single isomers. The interconversion of escin Ia and isoescin Ia when given alone indicates that administration of one isomer leads to exposure to the other.</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2011.11.003</identifier><identifier>PMID: 22094055</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>absorption ; active ingredients ; Administration, Oral ; Aesculus - chemistry ; Aesculus hippocastanum ; Animals ; Area Under Curve ; bioavailability ; Biological Availability ; Chromatography, Liquid ; computer software ; edema ; Escin - analogs & derivatives ; Escin - blood ; Escin - isolation & purification ; Escin - pharmacokinetics ; Escin Ia ; Female ; inflammation ; Injections, Intravenous ; Isoescin Ia ; isomers ; LC–MS/MS ; Male ; Pharmacokinetics ; Plant Extracts - blood ; Plant Extracts - pharmacokinetics ; Rat ; Rats ; Rats, Wistar ; seeds ; Seeds - chemistry ; sodium ; Sodium escinate ; statistical analysis ; Tandem Mass Spectrometry</subject><ispartof>Journal of ethnopharmacology, 2012-01, Vol.139 (1), p.201-206</ispartof><rights>2011 Elsevier Ireland Ltd</rights><rights>Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c291t-8016a8508e952fc8d4639fb4b75ee4b1322afcc86fe733c512ab743db030d96c3</citedby><cites>FETCH-LOGICAL-c291t-8016a8508e952fc8d4639fb4b75ee4b1322afcc86fe733c512ab743db030d96c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S037887411100794X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22094055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Xiu-Jun</creatorcontrib><creatorcontrib>Zhang, Meng-Liang</creatorcontrib><creatorcontrib>Cui, Xiang-Yong</creatorcontrib><creatorcontrib>Gao, Feng</creatorcontrib><creatorcontrib>He, Qun</creatorcontrib><creatorcontrib>Li, Xiao-Jiao</creatorcontrib><creatorcontrib>Zhang, Ji-Wen</creatorcontrib><creatorcontrib>Fawcett, J. Paul</creatorcontrib><creatorcontrib>Gu, Jing-Kai</creatorcontrib><title>Comparative pharmacokinetics and bioavailability of escin Ia and isoescin Ia after administration of escin and of pure escin Ia and isoescin Ia in rat</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>A study was carried out to investigate the pharmacokinetic properties of escin Ia and isoescin Ia in rats and the pharmacokinetic differences between sodium escinate and pure escin Ia and isoescin Ia. Their bidirectional intercoversion in vivo has not been previously reported.
Escin Ia and isoescin Ia have been traditionally used clinically as the chief active ingredients of escin, a major triterpene saponin isolated from horse chestnut (Aesculus hippocastanum) seeds for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema.
To establish a sensitive LC–MS/MS method and investigate the pharmacokinetic properties of escin Ia and isoescin Ia in rats and the pharmacokinetics difference of sodium escinate with pure escin Ia and isoescin Ia. The absolute bioavailability of escin Ia and isoescin Ia and the bidirectional interconversion of them in vivo were also scarcely reported.
Wister rats were administrated an intravenous (i.v.) dose (1.7mg/kg) of sodium escinate (corresponding to 0.5mg/kg of escin Ia and 0.5mg/kg of isoescin Ia, respectively) and an i.v. dose (0.5mg/kg) or oral dose (4mg/kg) of pure escin Ia or isoescin Ia, respectively. At different time points, the concentrations of escin Ia and isoescin Ia in rat plasma were determined by LC–MS/MS method. Main pharmacokinetic parameters including t1/2, MRT, CL, Vd, AUC and F were estimated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany) and statistical analysis was performed using the Student's t-test with P<0.05 as the level of significance.
After administration of sodium escinate, the t1/2 and MRT values for both escin Ia and isoescin Ia were larger than corresponding values for the compounds given alone. Absorption of escin Ia and isoescin Ia was very low with F values both <0.25%. Escin Ia and isoescin Ia were found to form the other isomer in vivo with the conversion of escin Ia to isoescin Ia being much extensive than from isoescin Ia to escin Ia.
Comparison of the pharmacokinetics of escin Ia and isoescin Ia given alone and together in rat suggest that administration of herbal preparations of escin for clinical use may provide longer duration of action than administration of single isomers. The interconversion of escin Ia and isoescin Ia when given alone indicates that administration of one isomer leads to exposure to the other.</description><subject>absorption</subject><subject>active ingredients</subject><subject>Administration, Oral</subject><subject>Aesculus - chemistry</subject><subject>Aesculus hippocastanum</subject><subject>Animals</subject><subject>Area Under Curve</subject><subject>bioavailability</subject><subject>Biological Availability</subject><subject>Chromatography, Liquid</subject><subject>computer software</subject><subject>edema</subject><subject>Escin - analogs & derivatives</subject><subject>Escin - blood</subject><subject>Escin - isolation & purification</subject><subject>Escin - pharmacokinetics</subject><subject>Escin Ia</subject><subject>Female</subject><subject>inflammation</subject><subject>Injections, Intravenous</subject><subject>Isoescin Ia</subject><subject>isomers</subject><subject>LC–MS/MS</subject><subject>Male</subject><subject>Pharmacokinetics</subject><subject>Plant Extracts - blood</subject><subject>Plant Extracts - pharmacokinetics</subject><subject>Rat</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>seeds</subject><subject>Seeds - chemistry</subject><subject>sodium</subject><subject>Sodium escinate</subject><subject>statistical analysis</subject><subject>Tandem Mass Spectrometry</subject><issn>0378-8741</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS3Uig6FB-gGsusqU_9lbKuralSgUqUuoGvrxrkGT5M4tTMj9UV4XjxMoSsqXdm68neOrHMIOWN0yShbXWyWG5yWnDK2LEOpeEMWTCteq0aJI7KgQulaK8lOyLucN5RSxSR9S044p0bSplmQX-s4TJBgDjuspp-QBnDxIYw4B5crGLuqDRF2EHpoQx_mpyr6CrMLY3UDf95Dji-7nzFV0A1hDHneu8bxRbCnyzJtE_7fopxF954ce-gzfni-T8n95-vv66_17d2Xm_XVbe24YXOtSwqgG6rRNNw73cmVML6VrWoQZcsE5-Cd0yuPSgjXMA6tkqJrqaCdWTlxSs4PvlOKj1vMsx1Cdtj3MGLcZmsYM9JoSQvJDqRLMeeE3k4pDJCeLKN234bd2NKG3bdhy5Q2iubjs_u2HbD7p_gbfwE-HQAP0cKPFLK9_1YcZKlKaslMIS4PBJYUdgGTLUHh6LALCd1suxhe-cBv0U6lUw</recordid><startdate>20120106</startdate><enddate>20120106</enddate><creator>Wu, Xiu-Jun</creator><creator>Zhang, Meng-Liang</creator><creator>Cui, Xiang-Yong</creator><creator>Gao, Feng</creator><creator>He, Qun</creator><creator>Li, Xiao-Jiao</creator><creator>Zhang, Ji-Wen</creator><creator>Fawcett, J. Paul</creator><creator>Gu, Jing-Kai</creator><general>Elsevier Ireland Ltd</general><scope>FBQ</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>20120106</creationdate><title>Comparative pharmacokinetics and bioavailability of escin Ia and isoescin Ia after administration of escin and of pure escin Ia and isoescin Ia in rat</title><author>Wu, Xiu-Jun ; Zhang, Meng-Liang ; Cui, Xiang-Yong ; Gao, Feng ; He, Qun ; Li, Xiao-Jiao ; Zhang, Ji-Wen ; Fawcett, J. Paul ; Gu, Jing-Kai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c291t-8016a8508e952fc8d4639fb4b75ee4b1322afcc86fe733c512ab743db030d96c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>absorption</topic><topic>active ingredients</topic><topic>Administration, Oral</topic><topic>Aesculus - chemistry</topic><topic>Aesculus hippocastanum</topic><topic>Animals</topic><topic>Area Under Curve</topic><topic>bioavailability</topic><topic>Biological Availability</topic><topic>Chromatography, Liquid</topic><topic>computer software</topic><topic>edema</topic><topic>Escin - analogs & derivatives</topic><topic>Escin - blood</topic><topic>Escin - isolation & purification</topic><topic>Escin - pharmacokinetics</topic><topic>Escin Ia</topic><topic>Female</topic><topic>inflammation</topic><topic>Injections, Intravenous</topic><topic>Isoescin Ia</topic><topic>isomers</topic><topic>LC–MS/MS</topic><topic>Male</topic><topic>Pharmacokinetics</topic><topic>Plant Extracts - blood</topic><topic>Plant Extracts - pharmacokinetics</topic><topic>Rat</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>seeds</topic><topic>Seeds - chemistry</topic><topic>sodium</topic><topic>Sodium escinate</topic><topic>statistical analysis</topic><topic>Tandem Mass Spectrometry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Xiu-Jun</creatorcontrib><creatorcontrib>Zhang, Meng-Liang</creatorcontrib><creatorcontrib>Cui, Xiang-Yong</creatorcontrib><creatorcontrib>Gao, Feng</creatorcontrib><creatorcontrib>He, Qun</creatorcontrib><creatorcontrib>Li, Xiao-Jiao</creatorcontrib><creatorcontrib>Zhang, Ji-Wen</creatorcontrib><creatorcontrib>Fawcett, J. Paul</creatorcontrib><creatorcontrib>Gu, Jing-Kai</creatorcontrib><collection>AGRIS</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 ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Xiu-Jun</au><au>Zhang, Meng-Liang</au><au>Cui, Xiang-Yong</au><au>Gao, Feng</au><au>He, Qun</au><au>Li, Xiao-Jiao</au><au>Zhang, Ji-Wen</au><au>Fawcett, J. Paul</au><au>Gu, Jing-Kai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative pharmacokinetics and bioavailability of escin Ia and isoescin Ia after administration of escin and of pure escin Ia and isoescin Ia in rat</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2012-01-06</date><risdate>2012</risdate><volume>139</volume><issue>1</issue><spage>201</spage><epage>206</epage><pages>201-206</pages><issn>0378-8741</issn><eissn>1872-7573</eissn><abstract>A study was carried out to investigate the pharmacokinetic properties of escin Ia and isoescin Ia in rats and the pharmacokinetic differences between sodium escinate and pure escin Ia and isoescin Ia. Their bidirectional intercoversion in vivo has not been previously reported.
Escin Ia and isoescin Ia have been traditionally used clinically as the chief active ingredients of escin, a major triterpene saponin isolated from horse chestnut (Aesculus hippocastanum) seeds for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema.
To establish a sensitive LC–MS/MS method and investigate the pharmacokinetic properties of escin Ia and isoescin Ia in rats and the pharmacokinetics difference of sodium escinate with pure escin Ia and isoescin Ia. The absolute bioavailability of escin Ia and isoescin Ia and the bidirectional interconversion of them in vivo were also scarcely reported.
Wister rats were administrated an intravenous (i.v.) dose (1.7mg/kg) of sodium escinate (corresponding to 0.5mg/kg of escin Ia and 0.5mg/kg of isoescin Ia, respectively) and an i.v. dose (0.5mg/kg) or oral dose (4mg/kg) of pure escin Ia or isoescin Ia, respectively. At different time points, the concentrations of escin Ia and isoescin Ia in rat plasma were determined by LC–MS/MS method. Main pharmacokinetic parameters including t1/2, MRT, CL, Vd, AUC and F were estimated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany) and statistical analysis was performed using the Student's t-test with P<0.05 as the level of significance.
After administration of sodium escinate, the t1/2 and MRT values for both escin Ia and isoescin Ia were larger than corresponding values for the compounds given alone. Absorption of escin Ia and isoescin Ia was very low with F values both <0.25%. Escin Ia and isoescin Ia were found to form the other isomer in vivo with the conversion of escin Ia to isoescin Ia being much extensive than from isoescin Ia to escin Ia.
Comparison of the pharmacokinetics of escin Ia and isoescin Ia given alone and together in rat suggest that administration of herbal preparations of escin for clinical use may provide longer duration of action than administration of single isomers. The interconversion of escin Ia and isoescin Ia when given alone indicates that administration of one isomer leads to exposure to the other.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>22094055</pmid><doi>10.1016/j.jep.2011.11.003</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0378-8741 |
| ispartof | Journal of ethnopharmacology, 2012-01, Vol.139 (1), p.201-206 |
| issn | 0378-8741 1872-7573 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_911949840 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | absorption active ingredients Administration, Oral Aesculus - chemistry Aesculus hippocastanum Animals Area Under Curve bioavailability Biological Availability Chromatography, Liquid computer software edema Escin - analogs & derivatives Escin - blood Escin - isolation & purification Escin - pharmacokinetics Escin Ia Female inflammation Injections, Intravenous Isoescin Ia isomers LC–MS/MS Male Pharmacokinetics Plant Extracts - blood Plant Extracts - pharmacokinetics Rat Rats Rats, Wistar seeds Seeds - chemistry sodium Sodium escinate statistical analysis Tandem Mass Spectrometry |
| title | Comparative pharmacokinetics and bioavailability of escin Ia and isoescin Ia after administration of escin and of pure escin Ia and isoescin Ia in rat |
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