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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Veröffentlicht in:Xenobiotica 1997, Vol.27 (1), p.73-85
Hauptverfasser: 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.
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container_end_page 85
container_issue 1
container_start_page 73
container_title Xenobiotica
container_volume 27
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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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. 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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$$Ginformahealthcare$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/004982597240776$$EHTML$$P50$$Ginformahealthcare$$H</linktohtml><link.rule.ids>315,781,785,4025,27928,27929,27930,59652,59758,60441,60547,61226,61261,61407,61442</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;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 &amp; 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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