Cholestasis in the rat by means of intravenous administration of cyclosporine vehicle, Cremophor EL
The effect of cyclosporine vehicle, Cremophor EL, on bile flow and biliary bile acids and bilirubin output was studied in anesthetized male Wistar rats. Intravenous administration of Cremophor EL or castor oil as a single bolus reduced bile flow and the biliary output of bile acids and bilirubin. Th...
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| Veröffentlicht in: | Transplantation 1989-10, Vol.48 (4), p.554-558 |
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| creator | ROMAN, I. D MONTE, M. J ESTELLER, A JIMENET, R |
| description | The effect of cyclosporine vehicle, Cremophor EL, on bile flow and biliary bile acids and bilirubin output was studied in anesthetized male Wistar rats. Intravenous administration of Cremophor EL or castor oil as a single bolus reduced bile flow and the biliary output of bile acids and bilirubin. The Cremophor EL-induced cholestasis was an immediate and reversible phenomenon, since at 30-35 min after drug injection all parameters evaluated had returned to control values. A slight increase in serum bilirubin concentrations was observed. Our data indicate that the observed cholestasis is related to a reduction in both bile acid-dependent and bile acid-independent bile flow, probably due to a transitory hepatotoxic effect of Cremophor EL. We conclude that the clinically used vehicle for i.v. administration of cyclosporine, Cremophor EL, has adverse effects on hepatobiliary physiology in the rat and suggest that an alternative vehicle should be used. |
| doi_str_mv | 10.1097/00007890-198910000-00003 |
| format | Article |
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D ; MONTE, M. J ; ESTELLER, A ; JIMENET, R</creator><creatorcontrib>ROMAN, I. D ; MONTE, M. J ; ESTELLER, A ; JIMENET, R</creatorcontrib><description>The effect of cyclosporine vehicle, Cremophor EL, on bile flow and biliary bile acids and bilirubin output was studied in anesthetized male Wistar rats. Intravenous administration of Cremophor EL or castor oil as a single bolus reduced bile flow and the biliary output of bile acids and bilirubin. The Cremophor EL-induced cholestasis was an immediate and reversible phenomenon, since at 30-35 min after drug injection all parameters evaluated had returned to control values. A slight increase in serum bilirubin concentrations was observed. Our data indicate that the observed cholestasis is related to a reduction in both bile acid-dependent and bile acid-independent bile flow, probably due to a transitory hepatotoxic effect of Cremophor EL. We conclude that the clinically used vehicle for i.v. administration of cyclosporine, Cremophor EL, has adverse effects on hepatobiliary physiology in the rat and suggest that an alternative vehicle should be used.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/00007890-198910000-00003</identifier><identifier>PMID: 2799907</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Animals ; Bile Acids and Salts - metabolism ; Bilirubin - metabolism ; Biological and medical sciences ; Cholestasis - chemically induced ; Cyclosporins - administration & dosage ; Drug toxicity and drugs side effects treatment ; Glycerol - analogs & derivatives ; Glycerol - toxicity ; Medical sciences ; Pharmaceutical Vehicles - adverse effects ; Pharmacology. Drug treatments ; Rats ; Secretory Rate - drug effects ; Toxicity: digestive system</subject><ispartof>Transplantation, 1989-10, Vol.48 (4), p.554-558</ispartof><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-bcba2f43fe50ac1e7a589e7605bdfff83874bf80b579c0df56f96aea881a720d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19736632$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2799907$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ROMAN, I. D</creatorcontrib><creatorcontrib>MONTE, M. J</creatorcontrib><creatorcontrib>ESTELLER, A</creatorcontrib><creatorcontrib>JIMENET, R</creatorcontrib><title>Cholestasis in the rat by means of intravenous administration of cyclosporine vehicle, Cremophor EL</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>The effect of cyclosporine vehicle, Cremophor EL, on bile flow and biliary bile acids and bilirubin output was studied in anesthetized male Wistar rats. Intravenous administration of Cremophor EL or castor oil as a single bolus reduced bile flow and the biliary output of bile acids and bilirubin. The Cremophor EL-induced cholestasis was an immediate and reversible phenomenon, since at 30-35 min after drug injection all parameters evaluated had returned to control values. A slight increase in serum bilirubin concentrations was observed. Our data indicate that the observed cholestasis is related to a reduction in both bile acid-dependent and bile acid-independent bile flow, probably due to a transitory hepatotoxic effect of Cremophor EL. We conclude that the clinically used vehicle for i.v. administration of cyclosporine, Cremophor EL, has adverse effects on hepatobiliary physiology in the rat and suggest that an alternative vehicle should be used.</description><subject>Animals</subject><subject>Bile Acids and Salts - metabolism</subject><subject>Bilirubin - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cholestasis - chemically induced</subject><subject>Cyclosporins - administration & dosage</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Glycerol - analogs & derivatives</subject><subject>Glycerol - toxicity</subject><subject>Medical sciences</subject><subject>Pharmaceutical Vehicles - adverse effects</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Secretory Rate - drug effects</subject><subject>Toxicity: digestive system</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFUEtPxCAQJkaj6-MnmHDRk1UopcDRbNZHsokXPTdTOmQxbVmhu8n-e1td1zkwme8xwEcI5eyeM6Me2FhKG5Zxow2fpmw6xBGZcSmKrGSaHZMZYwXPuBDqjJyn9DkqpFDqlJzmyhjD1IzY-Sq0mAZIPlHf02GFNMJA6x3tEPpEgxvhIcIW-7BJFJrO9z6NwOBDP7F2Z9uQ1iH6HukWV962eEfnEbuwXoVIF8tLcuKgTXi17xfk42nxPn_Jlm_Pr_PHZWaLnA9ZbWvIXSEcSgaWowKpDaqSybpxzmmhVVE7zWqpjGWNk6UzJSBozUHlrBEX5PZ37zqGr834qarzyWLbQo_j2ysui7w0UoxC_Su0MaQU0VXr6DuIu4qzasq3-su3OuT7A03W6_0dm7rD5mDcBzryN3sekoXWReitT__7jRJlKXLxDQ--hIM</recordid><startdate>19891001</startdate><enddate>19891001</enddate><creator>ROMAN, I. D</creator><creator>MONTE, M. 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J ; ESTELLER, A ; JIMENET, R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-bcba2f43fe50ac1e7a589e7605bdfff83874bf80b579c0df56f96aea881a720d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1989</creationdate><topic>Animals</topic><topic>Bile Acids and Salts - metabolism</topic><topic>Bilirubin - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cholestasis - chemically induced</topic><topic>Cyclosporins - administration & dosage</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Glycerol - analogs & derivatives</topic><topic>Glycerol - toxicity</topic><topic>Medical sciences</topic><topic>Pharmaceutical Vehicles - adverse effects</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Secretory Rate - drug effects</topic><topic>Toxicity: digestive system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ROMAN, I. D</creatorcontrib><creatorcontrib>MONTE, M. J</creatorcontrib><creatorcontrib>ESTELLER, A</creatorcontrib><creatorcontrib>JIMENET, R</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>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ROMAN, I. D</au><au>MONTE, M. J</au><au>ESTELLER, A</au><au>JIMENET, R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cholestasis in the rat by means of intravenous administration of cyclosporine vehicle, Cremophor EL</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>1989-10-01</date><risdate>1989</risdate><volume>48</volume><issue>4</issue><spage>554</spage><epage>558</epage><pages>554-558</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>The effect of cyclosporine vehicle, Cremophor EL, on bile flow and biliary bile acids and bilirubin output was studied in anesthetized male Wistar rats. Intravenous administration of Cremophor EL or castor oil as a single bolus reduced bile flow and the biliary output of bile acids and bilirubin. The Cremophor EL-induced cholestasis was an immediate and reversible phenomenon, since at 30-35 min after drug injection all parameters evaluated had returned to control values. A slight increase in serum bilirubin concentrations was observed. Our data indicate that the observed cholestasis is related to a reduction in both bile acid-dependent and bile acid-independent bile flow, probably due to a transitory hepatotoxic effect of Cremophor EL. We conclude that the clinically used vehicle for i.v. administration of cyclosporine, Cremophor EL, has adverse effects on hepatobiliary physiology in the rat and suggest that an alternative vehicle should be used.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>2799907</pmid><doi>10.1097/00007890-198910000-00003</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Transplantation, 1989-10, Vol.48 (4), p.554-558 |
| issn | 0041-1337 1534-6080 |
| language | eng |
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| source | MEDLINE; Journals@Ovid Complete |
| subjects | Animals Bile Acids and Salts - metabolism Bilirubin - metabolism Biological and medical sciences Cholestasis - chemically induced Cyclosporins - administration & dosage Drug toxicity and drugs side effects treatment Glycerol - analogs & derivatives Glycerol - toxicity Medical sciences Pharmaceutical Vehicles - adverse effects Pharmacology. Drug treatments Rats Secretory Rate - drug effects Toxicity: digestive system |
| title | Cholestasis in the rat by means of intravenous administration of cyclosporine vehicle, Cremophor EL |
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