Methotrexate and 7-hydroxy-methotrexate pharmacokinetics following intravenous bolus administration and high-dose infusion of methotrexate
The pharmacokinetics of methotrexate and 7-hydroxy-methotrexate were studied in patients undergoing very high-dose methotrexate monotherapy. The patients received, first, two methotrexate intravenous bolus test doses (50 mg/m 2 ) one with and one without concomitant administration of folinic acid (1...
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| Veröffentlicht in: | European journal of cancer & clinical oncology 1987-09, Vol.23 (9), p.1385-1390 |
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| container_title | European journal of cancer & clinical oncology |
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| creator | Bore, Patrick Bruno, Rene Lena, Nicole Favre, Roger Cano, Jean Paul |
| description | The pharmacokinetics of methotrexate and 7-hydroxy-methotrexate were studied in patients undergoing very high-dose methotrexate monotherapy. The patients received, first, two methotrexate intravenous bolus test doses (50
mg/m
2
) one with and one without concomitant administration of folinic acid (15
mg every 6
h) in a random sequence, and, second, an 8
h infusion, individualized to achieve a peak plasma concentration of 5 × 10
−4
M methotrexate (infusion rates > 1000
mg/h). Methotrexate and 7-hydroxy-methotrexate concentrations were measured by specific radioimmunoassays and the data were analysed simultaneously by an integrated pharmacokinetic model. Following test dose administration, methotrexate and 7-hydroxy-methotrexate plasma concentration kinetics were best described by assuming that methotexate elimination (and 7-hydroxy-methotrexate formation) occurred from a peripheral compartment reaching rapid equilibrium with the plasma. Folinic acid administration did not influence the disposition of either compound. Following the infusion, a significant (
P < 0.01) decrease of methotrexate total plasmatic clearance occurred without modification of 7-hydroxy-methotrexate formation and elimination. |
| doi_str_mv | 10.1016/0277-5379(87)90124-6 |
| format | Article |
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mg/m
2
) one with and one without concomitant administration of folinic acid (15
mg every 6
h) in a random sequence, and, second, an 8
h infusion, individualized to achieve a peak plasma concentration of 5 × 10
−4
M methotrexate (infusion rates > 1000
mg/h). Methotrexate and 7-hydroxy-methotrexate concentrations were measured by specific radioimmunoassays and the data were analysed simultaneously by an integrated pharmacokinetic model. Following test dose administration, methotrexate and 7-hydroxy-methotrexate plasma concentration kinetics were best described by assuming that methotexate elimination (and 7-hydroxy-methotrexate formation) occurred from a peripheral compartment reaching rapid equilibrium with the plasma. Folinic acid administration did not influence the disposition of either compound. Following the infusion, a significant (
P < 0.01) decrease of methotrexate total plasmatic clearance occurred without modification of 7-hydroxy-methotrexate formation and elimination.</description><identifier>ISSN: 0277-5379</identifier><identifier>DOI: 10.1016/0277-5379(87)90124-6</identifier><identifier>PMID: 3500051</identifier><identifier>CODEN: EJCODS</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Antineoplastic agents ; Biological and medical sciences ; Chemotherapy ; Female ; Humans ; Infusions, Intravenous ; Injections, Intravenous ; Leucovorin - therapeutic use ; Male ; Medical sciences ; Methotrexate - administration & dosage ; Methotrexate - analogs & derivatives ; Methotrexate - blood ; Methotrexate - pharmacokinetics ; Middle Aged ; Models, Biological ; Pharmacology. Drug treatments ; Time Factors</subject><ispartof>European journal of cancer & clinical oncology, 1987-09, Vol.23 (9), p.1385-1390</ispartof><rights>1987</rights><rights>1988 INIST-CNRS</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-8edd3c71ffa3b92917458e2919e7fab535339bb068d579f8f17d6c57b3868d5b3</citedby><cites>FETCH-LOGICAL-c386t-8edd3c71ffa3b92917458e2919e7fab535339bb068d579f8f17d6c57b3868d5b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7384652$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3500051$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bore, Patrick</creatorcontrib><creatorcontrib>Bruno, Rene</creatorcontrib><creatorcontrib>Lena, Nicole</creatorcontrib><creatorcontrib>Favre, Roger</creatorcontrib><creatorcontrib>Cano, Jean Paul</creatorcontrib><title>Methotrexate and 7-hydroxy-methotrexate pharmacokinetics following intravenous bolus administration and high-dose infusion of methotrexate</title><title>European journal of cancer & clinical oncology</title><addtitle>Eur J Cancer Clin Oncol</addtitle><description>The pharmacokinetics of methotrexate and 7-hydroxy-methotrexate were studied in patients undergoing very high-dose methotrexate monotherapy. The patients received, first, two methotrexate intravenous bolus test doses (50
mg/m
2
) one with and one without concomitant administration of folinic acid (15
mg every 6
h) in a random sequence, and, second, an 8
h infusion, individualized to achieve a peak plasma concentration of 5 × 10
−4
M methotrexate (infusion rates > 1000
mg/h). Methotrexate and 7-hydroxy-methotrexate concentrations were measured by specific radioimmunoassays and the data were analysed simultaneously by an integrated pharmacokinetic model. Following test dose administration, methotrexate and 7-hydroxy-methotrexate plasma concentration kinetics were best described by assuming that methotexate elimination (and 7-hydroxy-methotrexate formation) occurred from a peripheral compartment reaching rapid equilibrium with the plasma. Folinic acid administration did not influence the disposition of either compound. Following the infusion, a significant (
P < 0.01) decrease of methotrexate total plasmatic clearance occurred without modification of 7-hydroxy-methotrexate formation and elimination.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Chemotherapy</subject><subject>Female</subject><subject>Humans</subject><subject>Infusions, Intravenous</subject><subject>Injections, Intravenous</subject><subject>Leucovorin - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Methotrexate - administration & dosage</subject><subject>Methotrexate - analogs & derivatives</subject><subject>Methotrexate - blood</subject><subject>Methotrexate - pharmacokinetics</subject><subject>Middle Aged</subject><subject>Models, Biological</subject><subject>Pharmacology. Drug treatments</subject><subject>Time Factors</subject><issn>0277-5379</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1987</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1u3CAUhVkkSvP3Bo3kRRW1C7dgjMGbSFHUNpFSddOsEYZLTGLDFJgk8wp56jKZ0SirbrjSOd-5wEHoI8FfCSbdN9xwXjPK-8-Cf-kxadq620OHO_kDOkrpAeNGtIweoAPKMMaMHKLXX5DHkCO8qAyV8qbi9bgyMbys6vm9tRhVnJUOj85DdjpVNkxTeHb-vnI-R_UEPixTNYSpnMrMzrtU5OyCf1s7uvuxNiFBwe0yreVgq_dXnKB9q6YEp9t5jO5-fP9zdV3f_v55c3V5W2squlwLMIZqTqxVdOibnvCWCSizB27VwCijtB8G3AnDeG-FJdx0mvGhpIs00GN0vtm7iOHvElKWs0sapkl5KF-QghDCSM8L2G5AHUNKEaxcRDeruJIEy3Xtct2vXPcrBZdvtcuuxM62-5fDDGYX2nZe_E9bXyWtJhuV1y7tME5F27GmYBcbDEoXTw6iTNqB12BcBJ2lCe7_7_gHw4ykxA</recordid><startdate>19870901</startdate><enddate>19870901</enddate><creator>Bore, Patrick</creator><creator>Bruno, Rene</creator><creator>Lena, Nicole</creator><creator>Favre, Roger</creator><creator>Cano, Jean Paul</creator><general>Elsevier Ltd</general><general>Pergamon Press</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></search><sort><creationdate>19870901</creationdate><title>Methotrexate and 7-hydroxy-methotrexate pharmacokinetics following intravenous bolus administration and high-dose infusion of methotrexate</title><author>Bore, Patrick ; Bruno, Rene ; Lena, Nicole ; Favre, Roger ; Cano, Jean Paul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-8edd3c71ffa3b92917458e2919e7fab535339bb068d579f8f17d6c57b3868d5b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1987</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Chemotherapy</topic><topic>Female</topic><topic>Humans</topic><topic>Infusions, Intravenous</topic><topic>Injections, Intravenous</topic><topic>Leucovorin - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methotrexate - administration & dosage</topic><topic>Methotrexate - analogs & derivatives</topic><topic>Methotrexate - blood</topic><topic>Methotrexate - pharmacokinetics</topic><topic>Middle Aged</topic><topic>Models, Biological</topic><topic>Pharmacology. Drug treatments</topic><topic>Time Factors</topic><toplevel>online_resources</toplevel><creatorcontrib>Bore, Patrick</creatorcontrib><creatorcontrib>Bruno, Rene</creatorcontrib><creatorcontrib>Lena, Nicole</creatorcontrib><creatorcontrib>Favre, Roger</creatorcontrib><creatorcontrib>Cano, Jean Paul</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>MEDLINE - Academic</collection><jtitle>European journal of cancer & clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bore, Patrick</au><au>Bruno, Rene</au><au>Lena, Nicole</au><au>Favre, Roger</au><au>Cano, Jean Paul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methotrexate and 7-hydroxy-methotrexate pharmacokinetics following intravenous bolus administration and high-dose infusion of methotrexate</atitle><jtitle>European journal of cancer & clinical oncology</jtitle><addtitle>Eur J Cancer Clin Oncol</addtitle><date>1987-09-01</date><risdate>1987</risdate><volume>23</volume><issue>9</issue><spage>1385</spage><epage>1390</epage><pages>1385-1390</pages><issn>0277-5379</issn><coden>EJCODS</coden><abstract>The pharmacokinetics of methotrexate and 7-hydroxy-methotrexate were studied in patients undergoing very high-dose methotrexate monotherapy. The patients received, first, two methotrexate intravenous bolus test doses (50
mg/m
2
) one with and one without concomitant administration of folinic acid (15
mg every 6
h) in a random sequence, and, second, an 8
h infusion, individualized to achieve a peak plasma concentration of 5 × 10
−4
M methotrexate (infusion rates > 1000
mg/h). Methotrexate and 7-hydroxy-methotrexate concentrations were measured by specific radioimmunoassays and the data were analysed simultaneously by an integrated pharmacokinetic model. Following test dose administration, methotrexate and 7-hydroxy-methotrexate plasma concentration kinetics were best described by assuming that methotexate elimination (and 7-hydroxy-methotrexate formation) occurred from a peripheral compartment reaching rapid equilibrium with the plasma. Folinic acid administration did not influence the disposition of either compound. Following the infusion, a significant (
P < 0.01) decrease of methotrexate total plasmatic clearance occurred without modification of 7-hydroxy-methotrexate formation and elimination.</abstract><cop>Oxford</cop><cop>New York, NY</cop><pub>Elsevier Ltd</pub><pmid>3500051</pmid><doi>10.1016/0277-5379(87)90124-6</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0277-5379 |
| ispartof | European journal of cancer & clinical oncology, 1987-09, Vol.23 (9), p.1385-1390 |
| issn | 0277-5379 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_81115197 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Antineoplastic agents Biological and medical sciences Chemotherapy Female Humans Infusions, Intravenous Injections, Intravenous Leucovorin - therapeutic use Male Medical sciences Methotrexate - administration & dosage Methotrexate - analogs & derivatives Methotrexate - blood Methotrexate - pharmacokinetics Middle Aged Models, Biological Pharmacology. Drug treatments Time Factors |
| title | Methotrexate and 7-hydroxy-methotrexate pharmacokinetics following intravenous bolus administration and high-dose infusion of methotrexate |
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