The pharmacokinetics of antipyrine and three of its metabolites in the rabbit : intravenous administration of pure metabolites
Antipyrine (AP) is a commonly used probe of oxidative metabolism. Indirect evidence demonstrates formation rate limited disposition of its metabolites. Kinetic studies using antipyrine and its major metabolites 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA), and 4-hydroxyantipyrine (OHA) were...
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| Veröffentlicht in: | Pharmaceutical research 1991-12, Vol.8 (12), p.1470-1476 |
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| creator | PETER, J. V. S YUSUF ABUL-HAJJ AWNI, W. M |
| description | Antipyrine (AP) is a commonly used probe of oxidative metabolism. Indirect evidence demonstrates formation rate limited disposition of its metabolites. Kinetic studies using antipyrine and its major metabolites 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA), and 4-hydroxyantipyrine (OHA) were completed to investigate the metabolic fate of preformed antipyrine metabolite and to demonstrate directly formation rate-limited metabolite disposition in vivo. Bolus injections of antipyrine and preformed metabolites (40-50 mg/kg) were administered to male, New Zealand white rabbits. Plasma and urine were analyzed using HPLC. These studies demonstrate that HMA, NORA, and OHA are formation rate limited in the rabbit. NORA appears to undergo further extensive oxidative and conjugative metabolism. Unknown additional peaks were detected in urine after NORA dosing but not after HMA or OHA administration. Mass spectroscopy of the unknown HPLC eluents identified potential structures of these NORA metabolites. |
| doi_str_mv | 10.1023/A:1015830013451 |
| format | Article |
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V. S ; YUSUF ABUL-HAJJ ; AWNI, W. M</creator><creatorcontrib>PETER, J. V. S ; YUSUF ABUL-HAJJ ; AWNI, W. M</creatorcontrib><description>Antipyrine (AP) is a commonly used probe of oxidative metabolism. Indirect evidence demonstrates formation rate limited disposition of its metabolites. Kinetic studies using antipyrine and its major metabolites 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA), and 4-hydroxyantipyrine (OHA) were completed to investigate the metabolic fate of preformed antipyrine metabolite and to demonstrate directly formation rate-limited metabolite disposition in vivo. Bolus injections of antipyrine and preformed metabolites (40-50 mg/kg) were administered to male, New Zealand white rabbits. Plasma and urine were analyzed using HPLC. These studies demonstrate that HMA, NORA, and OHA are formation rate limited in the rabbit. NORA appears to undergo further extensive oxidative and conjugative metabolism. Unknown additional peaks were detected in urine after NORA dosing but not after HMA or OHA administration. Mass spectroscopy of the unknown HPLC eluents identified potential structures of these NORA metabolites.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/A:1015830013451</identifier><identifier>PMID: 1808608</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Animals ; Antipyrine - administration & dosage ; Antipyrine - analogs & derivatives ; Antipyrine - blood ; Antipyrine - pharmacokinetics ; Antipyrine - urine ; Biological and medical sciences ; Chromatography, High Pressure Liquid ; Edaravone ; General pharmacology ; Injections, Intravenous ; Male ; Mass Spectrometry ; Medical sciences ; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions ; Pharmacology. Drug treatments ; Rabbits</subject><ispartof>Pharmaceutical research, 1991-12, Vol.8 (12), p.1470-1476</ispartof><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c196t-ef3141c5f48d80aa2bcc082294f15e4dd0e73e6dfed32e3d9feb15f2972a28443</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5030739$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1808608$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PETER, J. V. S</creatorcontrib><creatorcontrib>YUSUF ABUL-HAJJ</creatorcontrib><creatorcontrib>AWNI, W. M</creatorcontrib><title>The pharmacokinetics of antipyrine and three of its metabolites in the rabbit : intravenous administration of pure metabolites</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>Antipyrine (AP) is a commonly used probe of oxidative metabolism. Indirect evidence demonstrates formation rate limited disposition of its metabolites. Kinetic studies using antipyrine and its major metabolites 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA), and 4-hydroxyantipyrine (OHA) were completed to investigate the metabolic fate of preformed antipyrine metabolite and to demonstrate directly formation rate-limited metabolite disposition in vivo. Bolus injections of antipyrine and preformed metabolites (40-50 mg/kg) were administered to male, New Zealand white rabbits. Plasma and urine were analyzed using HPLC. These studies demonstrate that HMA, NORA, and OHA are formation rate limited in the rabbit. NORA appears to undergo further extensive oxidative and conjugative metabolism. Unknown additional peaks were detected in urine after NORA dosing but not after HMA or OHA administration. Mass spectroscopy of the unknown HPLC eluents identified potential structures of these NORA metabolites.</description><subject>Animals</subject><subject>Antipyrine - administration & dosage</subject><subject>Antipyrine - analogs & derivatives</subject><subject>Antipyrine - blood</subject><subject>Antipyrine - pharmacokinetics</subject><subject>Antipyrine - urine</subject><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Edaravone</subject><subject>General pharmacology</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. Drug treatments</subject><subject>Rabbits</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkMtLAzEQxoMoWh9nT0IO4m118thu4q0UX1DwouCtZJMJje7LJBV68W93i0U8zcz3_b5hGELOGVwz4OJmdsuAlUoAMCFLtkcmrKxEoUG-7ZMJVFwWqpLsiByn9A4Aiml5SA6ZAjUFNSHfLyukw8rE1tj-I3SYg02099R0OQybOCpj62heRcStHnKiLWZT903ImGjoRg9pNHUdMr0d5xzNF3b9OlHj2tCFNAo59N02Pawj_o-fkgNvmoRnu3pCXu_vXuaPxeL54Wk-WxSW6Wku0AsmmS29VE6BMby2FhTnWnpWonQOsBI4dR6d4Cic9liz0nNdccOVlOKEXP3uHWL_ucaUl21IFpvGdDheuqz4VGsQfAQvduC6btEthxhaEzfL3cNG_3Lnm2RN46PpbEh_WAkCKqHFD3bffJ4</recordid><startdate>199112</startdate><enddate>199112</enddate><creator>PETER, J. V. S</creator><creator>YUSUF ABUL-HAJJ</creator><creator>AWNI, W. M</creator><general>Springer</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>199112</creationdate><title>The pharmacokinetics of antipyrine and three of its metabolites in the rabbit : intravenous administration of pure metabolites</title><author>PETER, J. V. S ; YUSUF ABUL-HAJJ ; AWNI, W. M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c196t-ef3141c5f48d80aa2bcc082294f15e4dd0e73e6dfed32e3d9feb15f2972a28443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Animals</topic><topic>Antipyrine - administration & dosage</topic><topic>Antipyrine - analogs & derivatives</topic><topic>Antipyrine - blood</topic><topic>Antipyrine - pharmacokinetics</topic><topic>Antipyrine - urine</topic><topic>Biological and medical sciences</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Edaravone</topic><topic>General pharmacology</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Rabbits</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PETER, J. V. S</creatorcontrib><creatorcontrib>YUSUF ABUL-HAJJ</creatorcontrib><creatorcontrib>AWNI, W. M</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>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PETER, J. V. S</au><au>YUSUF ABUL-HAJJ</au><au>AWNI, W. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The pharmacokinetics of antipyrine and three of its metabolites in the rabbit : intravenous administration of pure metabolites</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>1991-12</date><risdate>1991</risdate><volume>8</volume><issue>12</issue><spage>1470</spage><epage>1476</epage><pages>1470-1476</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Antipyrine (AP) is a commonly used probe of oxidative metabolism. Indirect evidence demonstrates formation rate limited disposition of its metabolites. Kinetic studies using antipyrine and its major metabolites 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA), and 4-hydroxyantipyrine (OHA) were completed to investigate the metabolic fate of preformed antipyrine metabolite and to demonstrate directly formation rate-limited metabolite disposition in vivo. Bolus injections of antipyrine and preformed metabolites (40-50 mg/kg) were administered to male, New Zealand white rabbits. Plasma and urine were analyzed using HPLC. These studies demonstrate that HMA, NORA, and OHA are formation rate limited in the rabbit. NORA appears to undergo further extensive oxidative and conjugative metabolism. Unknown additional peaks were detected in urine after NORA dosing but not after HMA or OHA administration. Mass spectroscopy of the unknown HPLC eluents identified potential structures of these NORA metabolites.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>1808608</pmid><doi>10.1023/A:1015830013451</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0724-8741 |
| ispartof | Pharmaceutical research, 1991-12, Vol.8 (12), p.1470-1476 |
| issn | 0724-8741 1573-904X |
| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Animals Antipyrine - administration & dosage Antipyrine - analogs & derivatives Antipyrine - blood Antipyrine - pharmacokinetics Antipyrine - urine Biological and medical sciences Chromatography, High Pressure Liquid Edaravone General pharmacology Injections, Intravenous Male Mass Spectrometry Medical sciences Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Rabbits |
| title | The pharmacokinetics of antipyrine and three of its metabolites in the rabbit : intravenous administration of pure metabolites |
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