Tissue distribution and metabolism in rat of an ethynesulphonamide with filaricidal activity
1. The tissue distribution and metabolism of a new filaricidal agent P903 (N -\[(2- phenylethynyl)sulfonyl]morpholine) were studied in rat. 2. After s.c. administration of C and C P903, the Tmax in the bloodwas observed on day 2. Elimination was slow and 95% was bound to protein. Radioactivity was d...
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creator | Radembino, N. Dessalles, M.- C. Trouvin, J.-H. Loiseau, P. M. Gayral, P. Mahuzier, G. Rapp, M. Labarre, P. Godeneche, D. Madelmont, J.-C. Maurizis, J.-C. Veyre, A. Chabard, J.-L. |
description | 1. The tissue distribution and metabolism of a new filaricidal agent P903 (N -\[(2- phenylethynyl)sulfonyl]morpholine) were studied in rat. 2. After s.c. administration of C and C P903, the Tmax in the bloodwas observed on day 2. Elimination was slow and 95% was bound to protein. Radioactivity was distributed in the whole organism but particularly in erythrocytes and the lymphatic channel. Four days later, 60% of the radioactivity was excreted in urine and faeces at equal amounts and 15% remained at the injection point. 3. In all biological fluids tested no P903 was found but only its metabolites. 4. One principal metabolite, the N -\[(2-phenyloxo-2-ethane) sulphonyl] morpholine or oxosulphonamide was identified in blood, urine and faeces as compared with the reference compound by GC MS and NMR. This latter molecule was detected following hydrolysis by hydrochloric acid but not with beta glucuronidase sulphatase. 5. Unconjugated and conjugated oxosulphonamide represented 85% of the radio activity at all times tested in blood but only 38 and 35% respectively of urinary and faecal radioactivity on day 1 after the administration of the labelled drug. 6. Thus, P903 is rapidly converted toareactive metabolite, probably anoxirene, which is then conjugated with endogenous components toform conjugated oxosulphonamide and anunknown metabolite. The role ofthis reactive metabolite in antifilarialactivity seems to be very important in understanding the mechanism of action of P903. |
doi_str_mv | 10.1080/004982597240776 |
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M. ; Gayral, P. ; Mahuzier, G. ; Rapp, M. ; Labarre, P. ; Godeneche, D. ; Madelmont, J.-C. ; Maurizis, J.-C. ; Veyre, A. ; Chabard, J.-L.</creator><creatorcontrib>Radembino, N. ; Dessalles, M.- C. ; Trouvin, J.-H. ; Loiseau, P. M. ; Gayral, P. ; Mahuzier, G. ; Rapp, M. ; Labarre, P. ; Godeneche, D. ; Madelmont, J.-C. ; Maurizis, J.-C. ; Veyre, A. ; Chabard, J.-L.</creatorcontrib><description>1. The tissue distribution and metabolism of a new filaricidal agent P903 (N -\[(2- phenylethynyl)sulfonyl]morpholine) were studied in rat. 2. After s.c. administration of C and C P903, the Tmax in the bloodwas observed on day 2. Elimination was slow and 95% was bound to protein. Radioactivity was distributed in the whole organism but particularly in erythrocytes and the lymphatic channel. Four days later, 60% of the radioactivity was excreted in urine and faeces at equal amounts and 15% remained at the injection point. 3. In all biological fluids tested no P903 was found but only its metabolites. 4. One principal metabolite, the N -\[(2-phenyloxo-2-ethane) sulphonyl] morpholine or oxosulphonamide was identified in blood, urine and faeces as compared with the reference compound by GC MS and NMR. This latter molecule was detected following hydrolysis by hydrochloric acid but not with beta glucuronidase sulphatase. 5. Unconjugated and conjugated oxosulphonamide represented 85% of the radio activity at all times tested in blood but only 38 and 35% respectively of urinary and faecal radioactivity on day 1 after the administration of the labelled drug. 6. Thus, P903 is rapidly converted toareactive metabolite, probably anoxirene, which is then conjugated with endogenous components toform conjugated oxosulphonamide and anunknown metabolite. The role ofthis reactive metabolite in antifilarialactivity seems to be very important in understanding the mechanism of action of P903.</description><identifier>ISSN: 0049-8254</identifier><identifier>EISSN: 1366-5928</identifier><identifier>DOI: 10.1080/004982597240776</identifier><identifier>PMID: 9041680</identifier><identifier>CODEN: XENOBH</identifier><language>eng</language><publisher>London: Informa UK Ltd</publisher><subject>Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiparasitic agents ; Biological and medical sciences ; Chromatography, High Pressure Liquid ; Filaricides - blood ; Filaricides - metabolism ; Filaricides - pharmacokinetics ; Filaricides - urine ; Kinetics ; Magnetic Resonance Spectroscopy ; Male ; Mass Spectrometry ; Medical sciences ; Pharmacology. Drug treatments ; Protein Binding ; Rats ; Rats, Sprague-Dawley ; Scintillation Counting ; Sulfonamides - blood ; Sulfonamides - metabolism ; Sulfonamides - pharmacokinetics ; Sulfonamides - urine ; Tissue Distribution</subject><ispartof>Xenobiotica, 1997, Vol.27 (1), p.73-85</ispartof><rights>1997 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 1997</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-17b5f775f369f01eef613c417762e01176f05d3e0d66bba5c2901472088665403</citedby><cites>FETCH-LOGICAL-c453t-17b5f775f369f01eef613c417762e01176f05d3e0d66bba5c2901472088665403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1080/004982597240776$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/004982597240776$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>315,782,786,4026,27930,27931,27932,59654,59760,60443,60549,61228,61263,61409,61444</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2574085$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9041680$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Radembino, N.</creatorcontrib><creatorcontrib>Dessalles, M.- C.</creatorcontrib><creatorcontrib>Trouvin, J.-H.</creatorcontrib><creatorcontrib>Loiseau, P. M.</creatorcontrib><creatorcontrib>Gayral, P.</creatorcontrib><creatorcontrib>Mahuzier, G.</creatorcontrib><creatorcontrib>Rapp, M.</creatorcontrib><creatorcontrib>Labarre, P.</creatorcontrib><creatorcontrib>Godeneche, D.</creatorcontrib><creatorcontrib>Madelmont, J.-C.</creatorcontrib><creatorcontrib>Maurizis, J.-C.</creatorcontrib><creatorcontrib>Veyre, A.</creatorcontrib><creatorcontrib>Chabard, J.-L.</creatorcontrib><title>Tissue distribution and metabolism in rat of an ethynesulphonamide with filaricidal activity</title><title>Xenobiotica</title><addtitle>Xenobiotica</addtitle><description>1. The tissue distribution and metabolism of a new filaricidal agent P903 (N -\[(2- phenylethynyl)sulfonyl]morpholine) were studied in rat. 2. After s.c. administration of C and C P903, the Tmax in the bloodwas observed on day 2. Elimination was slow and 95% was bound to protein. Radioactivity was distributed in the whole organism but particularly in erythrocytes and the lymphatic channel. Four days later, 60% of the radioactivity was excreted in urine and faeces at equal amounts and 15% remained at the injection point. 3. In all biological fluids tested no P903 was found but only its metabolites. 4. One principal metabolite, the N -\[(2-phenyloxo-2-ethane) sulphonyl] morpholine or oxosulphonamide was identified in blood, urine and faeces as compared with the reference compound by GC MS and NMR. This latter molecule was detected following hydrolysis by hydrochloric acid but not with beta glucuronidase sulphatase. 5. Unconjugated and conjugated oxosulphonamide represented 85% of the radio activity at all times tested in blood but only 38 and 35% respectively of urinary and faecal radioactivity on day 1 after the administration of the labelled drug. 6. Thus, P903 is rapidly converted toareactive metabolite, probably anoxirene, which is then conjugated with endogenous components toform conjugated oxosulphonamide and anunknown metabolite. The role ofthis reactive metabolite in antifilarialactivity seems to be very important in understanding the mechanism of action of P903.</description><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiparasitic agents</subject><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Filaricides - blood</subject><subject>Filaricides - metabolism</subject><subject>Filaricides - pharmacokinetics</subject><subject>Filaricides - urine</subject><subject>Kinetics</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Binding</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Scintillation Counting</subject><subject>Sulfonamides - blood</subject><subject>Sulfonamides - metabolism</subject><subject>Sulfonamides - pharmacokinetics</subject><subject>Sulfonamides - urine</subject><subject>Tissue Distribution</subject><issn>0049-8254</issn><issn>1366-5928</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFrFTEUhUOx1Gd13ZWQhbgbe5NMkok7KbUKhW7qThgymYRJySTPJGN5_955vNeCQnF1F-c7l3PPReiCwCcCHVwCtKqjXEnagpTiBG0IE6Lhinav0GavNqvcvkZvSnkAAEEoPUNnCloiOtign_e-lMXi0Zea_bBUnyLWccSzrXpIwZcZ-4izrji5VcC2TrtoyxK2U4p69qPFj75O2Pmgszd-1AFrU_1vX3dv0anTodh3x3mOfny9vr_61tze3Xy_-nLbmJaz2hA5cCcld0woB8RaJwgzLVnvoRYIkcIBH5mFUYhh0NxQBaSVFLpOCN4CO0cfD3u3Of1abKn97IuxIeho01J62XWMUs7_CxKuBBNMreDlATQ5lZKt67fZzzrvegL9vvj-n-JXx_vj6mWY7fjMH5te9Q9HXRejg8s6Gl-eMcplC90-4ecD5qNLedaPKYexr3oXUn7ysJczqL_Mk9WhTkZn2z-kJcf1By_m_wMAXK6D</recordid><startdate>1997</startdate><enddate>1997</enddate><creator>Radembino, N.</creator><creator>Dessalles, M.- C.</creator><creator>Trouvin, J.-H.</creator><creator>Loiseau, P. M.</creator><creator>Gayral, P.</creator><creator>Mahuzier, G.</creator><creator>Rapp, M.</creator><creator>Labarre, P.</creator><creator>Godeneche, D.</creator><creator>Madelmont, J.-C.</creator><creator>Maurizis, J.-C.</creator><creator>Veyre, A.</creator><creator>Chabard, J.-L.</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><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>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>1997</creationdate><title>Tissue distribution and metabolism in rat of an ethynesulphonamide with filaricidal activity</title><author>Radembino, N. ; Dessalles, M.- C. ; Trouvin, J.-H. ; Loiseau, P. M. ; Gayral, P. ; Mahuzier, G. ; Rapp, M. ; Labarre, P. ; Godeneche, D. ; Madelmont, J.-C. ; Maurizis, J.-C. ; Veyre, A. ; Chabard, J.-L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-17b5f775f369f01eef613c417762e01176f05d3e0d66bba5c2901472088665403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiparasitic agents</topic><topic>Biological and medical sciences</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Filaricides - blood</topic><topic>Filaricides - metabolism</topic><topic>Filaricides - pharmacokinetics</topic><topic>Filaricides - urine</topic><topic>Kinetics</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Binding</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Scintillation Counting</topic><topic>Sulfonamides - blood</topic><topic>Sulfonamides - metabolism</topic><topic>Sulfonamides - pharmacokinetics</topic><topic>Sulfonamides - urine</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Radembino, N.</creatorcontrib><creatorcontrib>Dessalles, M.- C.</creatorcontrib><creatorcontrib>Trouvin, J.-H.</creatorcontrib><creatorcontrib>Loiseau, P. M.</creatorcontrib><creatorcontrib>Gayral, P.</creatorcontrib><creatorcontrib>Mahuzier, G.</creatorcontrib><creatorcontrib>Rapp, M.</creatorcontrib><creatorcontrib>Labarre, P.</creatorcontrib><creatorcontrib>Godeneche, D.</creatorcontrib><creatorcontrib>Madelmont, J.-C.</creatorcontrib><creatorcontrib>Maurizis, J.-C.</creatorcontrib><creatorcontrib>Veyre, A.</creatorcontrib><creatorcontrib>Chabard, J.-L.</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Xenobiotica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Radembino, N.</au><au>Dessalles, M.- C.</au><au>Trouvin, J.-H.</au><au>Loiseau, P. M.</au><au>Gayral, P.</au><au>Mahuzier, G.</au><au>Rapp, M.</au><au>Labarre, P.</au><au>Godeneche, D.</au><au>Madelmont, J.-C.</au><au>Maurizis, J.-C.</au><au>Veyre, A.</au><au>Chabard, J.-L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tissue distribution and metabolism in rat of an ethynesulphonamide with filaricidal activity</atitle><jtitle>Xenobiotica</jtitle><addtitle>Xenobiotica</addtitle><date>1997</date><risdate>1997</risdate><volume>27</volume><issue>1</issue><spage>73</spage><epage>85</epage><pages>73-85</pages><issn>0049-8254</issn><eissn>1366-5928</eissn><coden>XENOBH</coden><abstract>1. The tissue distribution and metabolism of a new filaricidal agent P903 (N -\[(2- phenylethynyl)sulfonyl]morpholine) were studied in rat. 2. After s.c. administration of C and C P903, the Tmax in the bloodwas observed on day 2. Elimination was slow and 95% was bound to protein. Radioactivity was distributed in the whole organism but particularly in erythrocytes and the lymphatic channel. Four days later, 60% of the radioactivity was excreted in urine and faeces at equal amounts and 15% remained at the injection point. 3. In all biological fluids tested no P903 was found but only its metabolites. 4. One principal metabolite, the N -\[(2-phenyloxo-2-ethane) sulphonyl] morpholine or oxosulphonamide was identified in blood, urine and faeces as compared with the reference compound by GC MS and NMR. This latter molecule was detected following hydrolysis by hydrochloric acid but not with beta glucuronidase sulphatase. 5. Unconjugated and conjugated oxosulphonamide represented 85% of the radio activity at all times tested in blood but only 38 and 35% respectively of urinary and faecal radioactivity on day 1 after the administration of the labelled drug. 6. Thus, P903 is rapidly converted toareactive metabolite, probably anoxirene, which is then conjugated with endogenous components toform conjugated oxosulphonamide and anunknown metabolite. The role ofthis reactive metabolite in antifilarialactivity seems to be very important in understanding the mechanism of action of P903.</abstract><cop>London</cop><pub>Informa UK Ltd</pub><pmid>9041680</pmid><doi>10.1080/004982597240776</doi><tpages>13</tpages></addata></record> |
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source | MEDLINE; Taylor & Francis:Master (3349 titles); Taylor & Francis Medical Library - CRKN |
subjects | Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiparasitic agents Biological and medical sciences Chromatography, High Pressure Liquid Filaricides - blood Filaricides - metabolism Filaricides - pharmacokinetics Filaricides - urine Kinetics Magnetic Resonance Spectroscopy Male Mass Spectrometry Medical sciences Pharmacology. Drug treatments Protein Binding Rats Rats, Sprague-Dawley Scintillation Counting Sulfonamides - blood Sulfonamides - metabolism Sulfonamides - pharmacokinetics Sulfonamides - urine Tissue Distribution |
title | Tissue distribution and metabolism in rat of an ethynesulphonamide with filaricidal activity |
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