Mephenytoin stereoselective elimination in the rat: II. Comparison of mephenytoin stereoselective clearance during chronic intravenous and hepatic portal vein administration
The stereoselective clearances of R- and S-mephenytoin were determined in rats receiving either an intravenous or hepatic portal vein infusion of racemic mephenytoin. The mean +/- SD intravenous clearances of R- and S-mephenytoin were 1630 +/- 250 ml/hr and 630 +/- 250 ml/hr, respectively. The corre...
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| Veröffentlicht in: | European journal of drug metabolism and pharmacokinetics 1989-10, Vol.14 (4), p.269-278 |
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| creator | Akrawi, S H Wedlund, P J |
| description | The stereoselective clearances of R- and S-mephenytoin were determined in rats receiving either an intravenous or hepatic portal vein infusion of racemic mephenytoin. The mean +/- SD intravenous clearances of R- and S-mephenytoin were 1630 +/- 250 ml/hr and 630 +/- 250 ml/hr, respectively. The corresponding portal vein clearances for these enantiomers were 2560 +/- 1230 ml/hr (R-mephenytoin) and 540 +/- 230 ml/hr (S-mephenytoin). In spite of the slightly higher clearance for R-mephenytoin following portal vein administration, the difference between the intravenous and portal vein clearances for R- or S-mephenytoin were not found to be significant. Subsequent computer simulations of the data indicated there was less than a 5% probability that this result could be attributed solely to interanimal variability in drug clearance. The estimated extraction ratio of R-mephenytoin by the liver was modest and suggested mephenytoin may undergo a substantial degree of extrahepatic elimination in the rat. |
| doi_str_mv | 10.1007/BF03190110 |
| format | Article |
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Comparison of mephenytoin stereoselective clearance during chronic intravenous and hepatic portal vein administration</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Akrawi, S H ; Wedlund, P J</creator><creatorcontrib>Akrawi, S H ; Wedlund, P J</creatorcontrib><description>The stereoselective clearances of R- and S-mephenytoin were determined in rats receiving either an intravenous or hepatic portal vein infusion of racemic mephenytoin. The mean +/- SD intravenous clearances of R- and S-mephenytoin were 1630 +/- 250 ml/hr and 630 +/- 250 ml/hr, respectively. The corresponding portal vein clearances for these enantiomers were 2560 +/- 1230 ml/hr (R-mephenytoin) and 540 +/- 230 ml/hr (S-mephenytoin). In spite of the slightly higher clearance for R-mephenytoin following portal vein administration, the difference between the intravenous and portal vein clearances for R- or S-mephenytoin were not found to be significant. Subsequent computer simulations of the data indicated there was less than a 5% probability that this result could be attributed solely to interanimal variability in drug clearance. The estimated extraction ratio of R-mephenytoin by the liver was modest and suggested mephenytoin may undergo a substantial degree of extrahepatic elimination in the rat.</description><identifier>ISSN: 0378-7966</identifier><identifier>EISSN: 2107-0180</identifier><identifier>DOI: 10.1007/BF03190110</identifier><identifier>PMID: 2633921</identifier><language>eng</language><publisher>France</publisher><subject>Animals ; Blood Proteins - metabolism ; Chromatography, Gas ; Hydantoins - metabolism ; Hydantoins - pharmacokinetics ; Infusions, Intravenous ; Injections, Intravenous ; Liver - metabolism ; Male ; Mephenytoin - administration & dosage ; Mephenytoin - analogs & derivatives ; Mephenytoin - metabolism ; Mephenytoin - pharmacokinetics ; Portal Vein ; Protein Binding ; Rats ; Rats, Inbred Strains ; Stereoisomerism</subject><ispartof>European journal of drug metabolism and pharmacokinetics, 1989-10, Vol.14 (4), p.269-278</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c197t-aea6aa99b0167a8c90bd4ee8479a4b97e74ad12aa77d47dbb28dc00715dc322e3</citedby><cites>FETCH-LOGICAL-c197t-aea6aa99b0167a8c90bd4ee8479a4b97e74ad12aa77d47dbb28dc00715dc322e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2633921$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Akrawi, S H</creatorcontrib><creatorcontrib>Wedlund, P J</creatorcontrib><title>Mephenytoin stereoselective elimination in the rat: II. Comparison of mephenytoin stereoselective clearance during chronic intravenous and hepatic portal vein administration</title><title>European journal of drug metabolism and pharmacokinetics</title><addtitle>Eur J Drug Metab Pharmacokinet</addtitle><description>The stereoselective clearances of R- and S-mephenytoin were determined in rats receiving either an intravenous or hepatic portal vein infusion of racemic mephenytoin. The mean +/- SD intravenous clearances of R- and S-mephenytoin were 1630 +/- 250 ml/hr and 630 +/- 250 ml/hr, respectively. The corresponding portal vein clearances for these enantiomers were 2560 +/- 1230 ml/hr (R-mephenytoin) and 540 +/- 230 ml/hr (S-mephenytoin). In spite of the slightly higher clearance for R-mephenytoin following portal vein administration, the difference between the intravenous and portal vein clearances for R- or S-mephenytoin were not found to be significant. Subsequent computer simulations of the data indicated there was less than a 5% probability that this result could be attributed solely to interanimal variability in drug clearance. The estimated extraction ratio of R-mephenytoin by the liver was modest and suggested mephenytoin may undergo a substantial degree of extrahepatic elimination in the rat.</description><subject>Animals</subject><subject>Blood Proteins - metabolism</subject><subject>Chromatography, Gas</subject><subject>Hydantoins - metabolism</subject><subject>Hydantoins - pharmacokinetics</subject><subject>Infusions, Intravenous</subject><subject>Injections, Intravenous</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Mephenytoin - administration & dosage</subject><subject>Mephenytoin - analogs & derivatives</subject><subject>Mephenytoin - metabolism</subject><subject>Mephenytoin - pharmacokinetics</subject><subject>Portal Vein</subject><subject>Protein Binding</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Stereoisomerism</subject><issn>0378-7966</issn><issn>2107-0180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1L7DAUhoMoOqgb90JWLoRq0rRN4-46-DGguNF1OU3OOJE2qUlmwB_lfzTicN15Nlmch-e85CXkhLMLzpi8vL5lgivGOdshs5IzWTDesl0yY0K2hVRNc0COY3xjeUSr6rrZJ_tlI4Qq-Yx8PuK0QveRvHU0JgzoIw6ok90gxcGO1kGy3tG8TiukAdIVXSwu6NyPEwQb88ov6fiHRQ8IAZxGatbBuleqV8E7q7MyBdig8-tIwRm6winf0nTyIcFAN5hlYHICGzP4neKI7C1hiHi8fQ_Jy-3N8_y-eHi6W8z_PRSaK5kKQGgAlOoZbyS0WrHeVIhtJRVUvZIoKzC8BJDSVNL0fdkanf-S10aLskRxSM5-vFPw72uMqRtt1DgM4DCn7aSqeV3WIoPnP6AOPsaAy24KdoTw0XHWfdfT_daT4dOtdd2PaP6j2zLEFxGxj7E</recordid><startdate>198910</startdate><enddate>198910</enddate><creator>Akrawi, S H</creator><creator>Wedlund, P J</creator><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>198910</creationdate><title>Mephenytoin stereoselective elimination in the rat: II. Comparison of mephenytoin stereoselective clearance during chronic intravenous and hepatic portal vein administration</title><author>Akrawi, S H ; Wedlund, P J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c197t-aea6aa99b0167a8c90bd4ee8479a4b97e74ad12aa77d47dbb28dc00715dc322e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1989</creationdate><topic>Animals</topic><topic>Blood Proteins - metabolism</topic><topic>Chromatography, Gas</topic><topic>Hydantoins - metabolism</topic><topic>Hydantoins - pharmacokinetics</topic><topic>Infusions, Intravenous</topic><topic>Injections, Intravenous</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Mephenytoin - administration & dosage</topic><topic>Mephenytoin - analogs & derivatives</topic><topic>Mephenytoin - metabolism</topic><topic>Mephenytoin - pharmacokinetics</topic><topic>Portal Vein</topic><topic>Protein Binding</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Stereoisomerism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Akrawi, S H</creatorcontrib><creatorcontrib>Wedlund, P J</creatorcontrib><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>European journal of drug metabolism and pharmacokinetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akrawi, S H</au><au>Wedlund, P J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mephenytoin stereoselective elimination in the rat: II. Comparison of mephenytoin stereoselective clearance during chronic intravenous and hepatic portal vein administration</atitle><jtitle>European journal of drug metabolism and pharmacokinetics</jtitle><addtitle>Eur J Drug Metab Pharmacokinet</addtitle><date>1989-10</date><risdate>1989</risdate><volume>14</volume><issue>4</issue><spage>269</spage><epage>278</epage><pages>269-278</pages><issn>0378-7966</issn><eissn>2107-0180</eissn><abstract>The stereoselective clearances of R- and S-mephenytoin were determined in rats receiving either an intravenous or hepatic portal vein infusion of racemic mephenytoin. The mean +/- SD intravenous clearances of R- and S-mephenytoin were 1630 +/- 250 ml/hr and 630 +/- 250 ml/hr, respectively. The corresponding portal vein clearances for these enantiomers were 2560 +/- 1230 ml/hr (R-mephenytoin) and 540 +/- 230 ml/hr (S-mephenytoin). In spite of the slightly higher clearance for R-mephenytoin following portal vein administration, the difference between the intravenous and portal vein clearances for R- or S-mephenytoin were not found to be significant. Subsequent computer simulations of the data indicated there was less than a 5% probability that this result could be attributed solely to interanimal variability in drug clearance. The estimated extraction ratio of R-mephenytoin by the liver was modest and suggested mephenytoin may undergo a substantial degree of extrahepatic elimination in the rat.</abstract><cop>France</cop><pmid>2633921</pmid><doi>10.1007/BF03190110</doi><tpages>10</tpages></addata></record> |
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| identifier | ISSN: 0378-7966 |
| ispartof | European journal of drug metabolism and pharmacokinetics, 1989-10, Vol.14 (4), p.269-278 |
| issn | 0378-7966 2107-0180 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Animals Blood Proteins - metabolism Chromatography, Gas Hydantoins - metabolism Hydantoins - pharmacokinetics Infusions, Intravenous Injections, Intravenous Liver - metabolism Male Mephenytoin - administration & dosage Mephenytoin - analogs & derivatives Mephenytoin - metabolism Mephenytoin - pharmacokinetics Portal Vein Protein Binding Rats Rats, Inbred Strains Stereoisomerism |
| title | Mephenytoin stereoselective elimination in the rat: II. Comparison of mephenytoin stereoselective clearance during chronic intravenous and hepatic portal vein administration |
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