Metabolism of ifosfamide during a 3 day infusion
Urinary drug metabolites were measured in 21 patients receiving ifosfamide by continuous infusion over 3 days. Mean values for the proportion of drug excreted as parent compound, 2-dechloroethylifosfamide (2-DC), 3-dechloroethylifosfamide (3-DC), carboxyifosfamide (CX) and ifosforamide mustard (IPM)...
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| Veröffentlicht in: | British journal of cancer 1994-05, Vol.69 (5), p.931-936 |
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| container_title | British journal of cancer |
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| creator | HARTLEY, J. M HANSEN, L HARLAND, S. J NICHOLSON, P. W PASINI, F SOUHAMI, R. L |
| description | Urinary drug metabolites were measured in 21 patients receiving ifosfamide by continuous infusion over 3 days. Mean values for the proportion of drug excreted as parent compound, 2-dechloroethylifosfamide (2-DC), 3-dechloroethylifosfamide (3-DC), carboxyifosfamide (CX) and ifosforamide mustard (IPM) were 19, 6, 10, 7 and 8% of dose respectively. The proportion of urinary drug products in the form of ifosfamide fell considerably over the course of the 3 days. This was mirrored by an increase in the proportion of 2-DC, 3-DC and CX. The proportion in the form of IPM, however, remained unchanged. With successive cycles the amount of 2-DC and IPM increased by about 10% per course. A very wide variation in the amount of each metabolite was reproducibly seen between patients, but no evidence for a genetic polymorphism was found. Urinary dechloroethyl metabolites correlated positively with each other and negatively with CX. Although autoinduction increases 'activation' of ifosfamide when given over 3 days, our evidence suggests that competing metabolic pathways prevent an increase in the amount of active metabolite formed. |
| doi_str_mv | 10.1038/bjc.1994.180 |
| format | Article |
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M ; HANSEN, L ; HARLAND, S. J ; NICHOLSON, P. W ; PASINI, F ; SOUHAMI, R. L</creator><creatorcontrib>HARTLEY, J. M ; HANSEN, L ; HARLAND, S. J ; NICHOLSON, P. W ; PASINI, F ; SOUHAMI, R. L</creatorcontrib><description>Urinary drug metabolites were measured in 21 patients receiving ifosfamide by continuous infusion over 3 days. Mean values for the proportion of drug excreted as parent compound, 2-dechloroethylifosfamide (2-DC), 3-dechloroethylifosfamide (3-DC), carboxyifosfamide (CX) and ifosforamide mustard (IPM) were 19, 6, 10, 7 and 8% of dose respectively. The proportion of urinary drug products in the form of ifosfamide fell considerably over the course of the 3 days. This was mirrored by an increase in the proportion of 2-DC, 3-DC and CX. The proportion in the form of IPM, however, remained unchanged. With successive cycles the amount of 2-DC and IPM increased by about 10% per course. A very wide variation in the amount of each metabolite was reproducibly seen between patients, but no evidence for a genetic polymorphism was found. Urinary dechloroethyl metabolites correlated positively with each other and negatively with CX. Although autoinduction increases 'activation' of ifosfamide when given over 3 days, our evidence suggests that competing metabolic pathways prevent an increase in the amount of active metabolite formed.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.1994.180</identifier><identifier>PMID: 8180026</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Adenocarcinoma - urine ; Antineoplastic agents ; Biological and medical sciences ; Chemotherapy ; Chromatography, Thin Layer ; Female ; Humans ; Ifosfamide - administration & dosage ; Ifosfamide - analogs & derivatives ; Ifosfamide - metabolism ; Ifosfamide - urine ; Male ; Medical sciences ; Neuroectodermal Tumors, Primitive - urine ; Osteosarcoma - urine ; Pharmacology. Drug treatments ; Phosphoramide Mustards ; Rhabdomyosarcoma - urine ; Sarcoma, Ewing - urine ; Time Factors</subject><ispartof>British journal of cancer, 1994-05, Vol.69 (5), p.931-936</ispartof><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-2508168d3b2c6cf9bb33bdfa1bb32196ab80f16a3d849798f4a46d1043dd3533</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968912/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968912/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,2727,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4079838$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8180026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HARTLEY, J. M</creatorcontrib><creatorcontrib>HANSEN, L</creatorcontrib><creatorcontrib>HARLAND, S. J</creatorcontrib><creatorcontrib>NICHOLSON, P. W</creatorcontrib><creatorcontrib>PASINI, F</creatorcontrib><creatorcontrib>SOUHAMI, R. L</creatorcontrib><title>Metabolism of ifosfamide during a 3 day infusion</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><description>Urinary drug metabolites were measured in 21 patients receiving ifosfamide by continuous infusion over 3 days. Mean values for the proportion of drug excreted as parent compound, 2-dechloroethylifosfamide (2-DC), 3-dechloroethylifosfamide (3-DC), carboxyifosfamide (CX) and ifosforamide mustard (IPM) were 19, 6, 10, 7 and 8% of dose respectively. The proportion of urinary drug products in the form of ifosfamide fell considerably over the course of the 3 days. This was mirrored by an increase in the proportion of 2-DC, 3-DC and CX. The proportion in the form of IPM, however, remained unchanged. With successive cycles the amount of 2-DC and IPM increased by about 10% per course. A very wide variation in the amount of each metabolite was reproducibly seen between patients, but no evidence for a genetic polymorphism was found. Urinary dechloroethyl metabolites correlated positively with each other and negatively with CX. Although autoinduction increases 'activation' of ifosfamide when given over 3 days, our evidence suggests that competing metabolic pathways prevent an increase in the amount of active metabolite formed.</description><subject>Adenocarcinoma - urine</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Chemotherapy</subject><subject>Chromatography, Thin Layer</subject><subject>Female</subject><subject>Humans</subject><subject>Ifosfamide - administration & dosage</subject><subject>Ifosfamide - analogs & derivatives</subject><subject>Ifosfamide - metabolism</subject><subject>Ifosfamide - urine</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuroectodermal Tumors, Primitive - urine</subject><subject>Osteosarcoma - urine</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphoramide Mustards</subject><subject>Rhabdomyosarcoma - urine</subject><subject>Sarcoma, Ewing - urine</subject><subject>Time Factors</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEtLAzEUhYMotVZ3boVZiCunJpN0JtkIUnxBxU334U4eNWVmosmM0H9vakvR1c3lfJxzcxC6JHhKMOV39VpNiRBsSjg-QmMyo0VOeFEdozHGuMqxKPApOotxnVaBeTVCI55YXJRjhN9MD7VvXGwzbzNnfbTQOm0yPQTXrTLIaKZhk7nODtH57hydWGiiudjPCVo-PS7nL_ni_fl1_rDIFaO0z4sZ5qTkmtaFKpUVdU1prS2Q9CiIKKHm2JISqOZMVIJbBqzUBDOqNZ1ROkH3O9vPoW6NVqbrAzTyM7gWwkZ6cPK_0rkPufLfMnlzQYpkcLM3CP5rMLGXrYvKNA10xg9RViXjbEZ5Am93oAo-xmDsIYRguS1YpoLltmCZSkv41d_DDvC-0aRf73WIChoboFMuHjCG02d_U7Md1kE_BHPQU9Y2apv0A86sjcE</recordid><startdate>19940501</startdate><enddate>19940501</enddate><creator>HARTLEY, J. M</creator><creator>HANSEN, L</creator><creator>HARLAND, S. J</creator><creator>NICHOLSON, P. W</creator><creator>PASINI, F</creator><creator>SOUHAMI, R. L</creator><general>Nature Publishing Group</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>19940501</creationdate><title>Metabolism of ifosfamide during a 3 day infusion</title><author>HARTLEY, J. M ; HANSEN, L ; HARLAND, S. J ; NICHOLSON, P. W ; PASINI, F ; SOUHAMI, R. L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-2508168d3b2c6cf9bb33bdfa1bb32196ab80f16a3d849798f4a46d1043dd3533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Adenocarcinoma - urine</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Chemotherapy</topic><topic>Chromatography, Thin Layer</topic><topic>Female</topic><topic>Humans</topic><topic>Ifosfamide - administration & dosage</topic><topic>Ifosfamide - analogs & derivatives</topic><topic>Ifosfamide - metabolism</topic><topic>Ifosfamide - urine</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuroectodermal Tumors, Primitive - urine</topic><topic>Osteosarcoma - urine</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphoramide Mustards</topic><topic>Rhabdomyosarcoma - urine</topic><topic>Sarcoma, Ewing - urine</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HARTLEY, J. M</creatorcontrib><creatorcontrib>HANSEN, L</creatorcontrib><creatorcontrib>HARLAND, S. J</creatorcontrib><creatorcontrib>NICHOLSON, P. W</creatorcontrib><creatorcontrib>PASINI, F</creatorcontrib><creatorcontrib>SOUHAMI, R. 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L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolism of ifosfamide during a 3 day infusion</atitle><jtitle>British journal of cancer</jtitle><addtitle>Br J Cancer</addtitle><date>1994-05-01</date><risdate>1994</risdate><volume>69</volume><issue>5</issue><spage>931</spage><epage>936</epage><pages>931-936</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Urinary drug metabolites were measured in 21 patients receiving ifosfamide by continuous infusion over 3 days. Mean values for the proportion of drug excreted as parent compound, 2-dechloroethylifosfamide (2-DC), 3-dechloroethylifosfamide (3-DC), carboxyifosfamide (CX) and ifosforamide mustard (IPM) were 19, 6, 10, 7 and 8% of dose respectively. The proportion of urinary drug products in the form of ifosfamide fell considerably over the course of the 3 days. This was mirrored by an increase in the proportion of 2-DC, 3-DC and CX. The proportion in the form of IPM, however, remained unchanged. With successive cycles the amount of 2-DC and IPM increased by about 10% per course. A very wide variation in the amount of each metabolite was reproducibly seen between patients, but no evidence for a genetic polymorphism was found. Urinary dechloroethyl metabolites correlated positively with each other and negatively with CX. Although autoinduction increases 'activation' of ifosfamide when given over 3 days, our evidence suggests that competing metabolic pathways prevent an increase in the amount of active metabolite formed.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>8180026</pmid><doi>10.1038/bjc.1994.180</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma - urine Antineoplastic agents Biological and medical sciences Chemotherapy Chromatography, Thin Layer Female Humans Ifosfamide - administration & dosage Ifosfamide - analogs & derivatives Ifosfamide - metabolism Ifosfamide - urine Male Medical sciences Neuroectodermal Tumors, Primitive - urine Osteosarcoma - urine Pharmacology. Drug treatments Phosphoramide Mustards Rhabdomyosarcoma - urine Sarcoma, Ewing - urine Time Factors |
| title | Metabolism of ifosfamide during a 3 day infusion |
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