Pharmacokinetics and pharmacodynamics of intravenous epoetin alfa in children with cancer
Background Epoetin alfa (EPO, PROCRIT®) pharmacokinetics and pharmacodynamics were evaluated in children with malignant solid tumors receiving chemotherapy. Procedure Children initially received IV EPO 600 IU/kg (max dose 40,000 IU) or placebo once weekly for 16 weeks. Dose was increased to 900 IU/k...
Gespeichert in:
| Veröffentlicht in: | Pediatric blood & cancer 2006-10, Vol.47 (5), p.572-579 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 579 |
|---|---|
| container_issue | 5 |
| container_start_page | 572 |
| container_title | Pediatric blood & cancer |
| container_volume | 47 |
| creator | Freeman III, Burgess B. Hinds, Pamela Iacono, Lisa C. Razzouk, Bassem I. Burghen, Elizabeth Stewart, Clinton F. |
| description | Background
Epoetin alfa (EPO, PROCRIT®) pharmacokinetics and pharmacodynamics were evaluated in children with malignant solid tumors receiving chemotherapy.
Procedure
Children initially received IV EPO 600 IU/kg (max dose 40,000 IU) or placebo once weekly for 16 weeks. Dose was increased to 900 IU/kg (max dose 60,000 IU) for patients not achieving a 1 g/dl increase in hemoglobin by study week 3 or 4. Serial PK samples were collected for 24 hr after the first study dose, and after the 10th or 11th dose. Serum EPO concentrations were analyzed using an ELISA assay, and pharmacokinetics were evaluated using compartmental methods.
Results
Twelve children participated; six (median age 15.2 years; range 9.3–18.6 years) were randomized to receive EPO. All children required dosage increases to 900 IU/kg due to no response. The median (range) apparent EPO AUC0–24 and clearance (CL) were 67.1 IU/ml·hr (13.8–102.6) and 0.26 L/hr/m2 (0.19–1.08), respectively. After the 10th or 11th EPO dose in four of these six EPO patients, the median (range) apparent AUC0–24 and CL of EPO was 126.5 IU/ml·hr (107.3–161.1) and 0.21 L/hr/m2 (0.15–0.25), respectively. No significant correlations were observed between pharmacokinetic parameters and pharmacodynamic effects.
Conclusions
EPO disposition in our patients was similar to other pediatric patient populations or adults receiving IV EPO. Interesting but insignificant trends were noted in pharmacodynamic effects. Pediatr Blood Cancer 2006; 47:572–579. © 2005 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/pbc.20685 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68809056</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>68809056</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3915-8a76145cb53943120c4b4091fbe9d23c10a3d5068f7c089f2447bd329c1468853</originalsourceid><addsrcrecordid>eNp10E1PwyAYB3BiNDqnB7-A6UUTD3VQoLRHnTpNFp2JL9ELoZRmuJZW6Jz79jJX9eQJAr-Hh-cPwAGCpwjCaNBk8jSCcUI3QA9RQkMKEdv83cN0B-w69-ZpDGmyDXZQjBFjMeyBl8lU2ErIeqaNarV0gTB50HSH-dKIanVYF4E2rRUfytRzF6im9tgEoiyEvwjkVJe5VSZY6HYaSGGksntgqxClU_vd2gePV5cPw-twfDe6GZ6NQ4lTRMNEsBgRKjOKU4JRBCXJCExRkak0j7BEUOCc-uEKJmGSFhEhLMtxlEpE4iShuA-O1-82tn6fK9fySjupylIY5f_KPYIppLGHJ2sobe2cVQVvrK6EXXIE-SpH7nPk3zl6e9g9Os8qlf_JLjgPjjognPQxWD-zdn8ugYwygrwbrN1Cl2r5f0c-OR_-tA7XFdq16vO3QtgZjxlmlD_fjvg9ndxePDyN-Sv-AledmE8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68809056</pqid></control><display><type>article</type><title>Pharmacokinetics and pharmacodynamics of intravenous epoetin alfa in children with cancer</title><source>Wiley Online Library - AutoHoldings Journals</source><source>MEDLINE</source><creator>Freeman III, Burgess B. ; Hinds, Pamela ; Iacono, Lisa C. ; Razzouk, Bassem I. ; Burghen, Elizabeth ; Stewart, Clinton F.</creator><creatorcontrib>Freeman III, Burgess B. ; Hinds, Pamela ; Iacono, Lisa C. ; Razzouk, Bassem I. ; Burghen, Elizabeth ; Stewart, Clinton F.</creatorcontrib><description>Background
Epoetin alfa (EPO, PROCRIT®) pharmacokinetics and pharmacodynamics were evaluated in children with malignant solid tumors receiving chemotherapy.
Procedure
Children initially received IV EPO 600 IU/kg (max dose 40,000 IU) or placebo once weekly for 16 weeks. Dose was increased to 900 IU/kg (max dose 60,000 IU) for patients not achieving a 1 g/dl increase in hemoglobin by study week 3 or 4. Serial PK samples were collected for 24 hr after the first study dose, and after the 10th or 11th dose. Serum EPO concentrations were analyzed using an ELISA assay, and pharmacokinetics were evaluated using compartmental methods.
Results
Twelve children participated; six (median age 15.2 years; range 9.3–18.6 years) were randomized to receive EPO. All children required dosage increases to 900 IU/kg due to no response. The median (range) apparent EPO AUC0–24 and clearance (CL) were 67.1 IU/ml·hr (13.8–102.6) and 0.26 L/hr/m2 (0.19–1.08), respectively. After the 10th or 11th EPO dose in four of these six EPO patients, the median (range) apparent AUC0–24 and CL of EPO was 126.5 IU/ml·hr (107.3–161.1) and 0.21 L/hr/m2 (0.15–0.25), respectively. No significant correlations were observed between pharmacokinetic parameters and pharmacodynamic effects.
Conclusions
EPO disposition in our patients was similar to other pediatric patient populations or adults receiving IV EPO. Interesting but insignificant trends were noted in pharmacodynamic effects. Pediatr Blood Cancer 2006; 47:572–579. © 2005 Wiley‐Liss, Inc.</description><identifier>ISSN: 1545-5009</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.20685</identifier><identifier>PMID: 16317760</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adolescent ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Bone Neoplasms - drug therapy ; Child ; Chondrosarcoma - drug therapy ; Dose-Response Relationship, Drug ; Double-Blind Method ; Epoetin Alfa ; erythropoietin ; Erythropoietin - pharmacokinetics ; Erythropoietin - therapeutic use ; Female ; General aspects ; Hematinics - pharmacokinetics ; Hematinics - therapeutic use ; Humans ; Injections, Intravenous ; Male ; Medical sciences ; Melanoma - drug therapy ; Osteosarcoma - drug therapy ; pediatrics ; pharmacodynamics ; pharmacokinetics ; Placebos ; Recombinant Proteins ; Skin Neoplasms - drug therapy ; Time Factors ; Treatment Outcome ; Tumors</subject><ispartof>Pediatric blood & cancer, 2006-10, Vol.47 (5), p.572-579</ispartof><rights>Copyright © 2005 Wiley‐Liss, Inc.</rights><rights>2006 INIST-CNRS</rights><rights>Copyright (c) 2005 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3915-8a76145cb53943120c4b4091fbe9d23c10a3d5068f7c089f2447bd329c1468853</citedby><cites>FETCH-LOGICAL-c3915-8a76145cb53943120c4b4091fbe9d23c10a3d5068f7c089f2447bd329c1468853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpbc.20685$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpbc.20685$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18075741$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16317760$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Freeman III, Burgess B.</creatorcontrib><creatorcontrib>Hinds, Pamela</creatorcontrib><creatorcontrib>Iacono, Lisa C.</creatorcontrib><creatorcontrib>Razzouk, Bassem I.</creatorcontrib><creatorcontrib>Burghen, Elizabeth</creatorcontrib><creatorcontrib>Stewart, Clinton F.</creatorcontrib><title>Pharmacokinetics and pharmacodynamics of intravenous epoetin alfa in children with cancer</title><title>Pediatric blood & cancer</title><addtitle>Pediatr. Blood Cancer</addtitle><description>Background
Epoetin alfa (EPO, PROCRIT®) pharmacokinetics and pharmacodynamics were evaluated in children with malignant solid tumors receiving chemotherapy.
Procedure
Children initially received IV EPO 600 IU/kg (max dose 40,000 IU) or placebo once weekly for 16 weeks. Dose was increased to 900 IU/kg (max dose 60,000 IU) for patients not achieving a 1 g/dl increase in hemoglobin by study week 3 or 4. Serial PK samples were collected for 24 hr after the first study dose, and after the 10th or 11th dose. Serum EPO concentrations were analyzed using an ELISA assay, and pharmacokinetics were evaluated using compartmental methods.
Results
Twelve children participated; six (median age 15.2 years; range 9.3–18.6 years) were randomized to receive EPO. All children required dosage increases to 900 IU/kg due to no response. The median (range) apparent EPO AUC0–24 and clearance (CL) were 67.1 IU/ml·hr (13.8–102.6) and 0.26 L/hr/m2 (0.19–1.08), respectively. After the 10th or 11th EPO dose in four of these six EPO patients, the median (range) apparent AUC0–24 and CL of EPO was 126.5 IU/ml·hr (107.3–161.1) and 0.21 L/hr/m2 (0.15–0.25), respectively. No significant correlations were observed between pharmacokinetic parameters and pharmacodynamic effects.
Conclusions
EPO disposition in our patients was similar to other pediatric patient populations or adults receiving IV EPO. Interesting but insignificant trends were noted in pharmacodynamic effects. Pediatr Blood Cancer 2006; 47:572–579. © 2005 Wiley‐Liss, Inc.</description><subject>Adolescent</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Bone Neoplasms - drug therapy</subject><subject>Child</subject><subject>Chondrosarcoma - drug therapy</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Epoetin Alfa</subject><subject>erythropoietin</subject><subject>Erythropoietin - pharmacokinetics</subject><subject>Erythropoietin - therapeutic use</subject><subject>Female</subject><subject>General aspects</subject><subject>Hematinics - pharmacokinetics</subject><subject>Hematinics - therapeutic use</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Melanoma - drug therapy</subject><subject>Osteosarcoma - drug therapy</subject><subject>pediatrics</subject><subject>pharmacodynamics</subject><subject>pharmacokinetics</subject><subject>Placebos</subject><subject>Recombinant Proteins</subject><subject>Skin Neoplasms - drug therapy</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>1545-5009</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10E1PwyAYB3BiNDqnB7-A6UUTD3VQoLRHnTpNFp2JL9ELoZRmuJZW6Jz79jJX9eQJAr-Hh-cPwAGCpwjCaNBk8jSCcUI3QA9RQkMKEdv83cN0B-w69-ZpDGmyDXZQjBFjMeyBl8lU2ErIeqaNarV0gTB50HSH-dKIanVYF4E2rRUfytRzF6im9tgEoiyEvwjkVJe5VSZY6HYaSGGksntgqxClU_vd2gePV5cPw-twfDe6GZ6NQ4lTRMNEsBgRKjOKU4JRBCXJCExRkak0j7BEUOCc-uEKJmGSFhEhLMtxlEpE4iShuA-O1-82tn6fK9fySjupylIY5f_KPYIppLGHJ2sobe2cVQVvrK6EXXIE-SpH7nPk3zl6e9g9Os8qlf_JLjgPjjognPQxWD-zdn8ugYwygrwbrN1Cl2r5f0c-OR_-tA7XFdq16vO3QtgZjxlmlD_fjvg9ndxePDyN-Sv-AledmE8</recordid><startdate>20061015</startdate><enddate>20061015</enddate><creator>Freeman III, Burgess B.</creator><creator>Hinds, Pamela</creator><creator>Iacono, Lisa C.</creator><creator>Razzouk, Bassem I.</creator><creator>Burghen, Elizabeth</creator><creator>Stewart, Clinton F.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><scope>BSCLL</scope><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>20061015</creationdate><title>Pharmacokinetics and pharmacodynamics of intravenous epoetin alfa in children with cancer</title><author>Freeman III, Burgess B. ; Hinds, Pamela ; Iacono, Lisa C. ; Razzouk, Bassem I. ; Burghen, Elizabeth ; Stewart, Clinton F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3915-8a76145cb53943120c4b4091fbe9d23c10a3d5068f7c089f2447bd329c1468853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adolescent</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Bone Neoplasms - drug therapy</topic><topic>Child</topic><topic>Chondrosarcoma - drug therapy</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Epoetin Alfa</topic><topic>erythropoietin</topic><topic>Erythropoietin - pharmacokinetics</topic><topic>Erythropoietin - therapeutic use</topic><topic>Female</topic><topic>General aspects</topic><topic>Hematinics - pharmacokinetics</topic><topic>Hematinics - therapeutic use</topic><topic>Humans</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Melanoma - drug therapy</topic><topic>Osteosarcoma - drug therapy</topic><topic>pediatrics</topic><topic>pharmacodynamics</topic><topic>pharmacokinetics</topic><topic>Placebos</topic><topic>Recombinant Proteins</topic><topic>Skin Neoplasms - drug therapy</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Freeman III, Burgess B.</creatorcontrib><creatorcontrib>Hinds, Pamela</creatorcontrib><creatorcontrib>Iacono, Lisa C.</creatorcontrib><creatorcontrib>Razzouk, Bassem I.</creatorcontrib><creatorcontrib>Burghen, Elizabeth</creatorcontrib><creatorcontrib>Stewart, Clinton F.</creatorcontrib><collection>Istex</collection><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>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Freeman III, Burgess B.</au><au>Hinds, Pamela</au><au>Iacono, Lisa C.</au><au>Razzouk, Bassem I.</au><au>Burghen, Elizabeth</au><au>Stewart, Clinton F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics and pharmacodynamics of intravenous epoetin alfa in children with cancer</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr. Blood Cancer</addtitle><date>2006-10-15</date><risdate>2006</risdate><volume>47</volume><issue>5</issue><spage>572</spage><epage>579</epage><pages>572-579</pages><issn>1545-5009</issn><eissn>1545-5017</eissn><abstract>Background
Epoetin alfa (EPO, PROCRIT®) pharmacokinetics and pharmacodynamics were evaluated in children with malignant solid tumors receiving chemotherapy.
Procedure
Children initially received IV EPO 600 IU/kg (max dose 40,000 IU) or placebo once weekly for 16 weeks. Dose was increased to 900 IU/kg (max dose 60,000 IU) for patients not achieving a 1 g/dl increase in hemoglobin by study week 3 or 4. Serial PK samples were collected for 24 hr after the first study dose, and after the 10th or 11th dose. Serum EPO concentrations were analyzed using an ELISA assay, and pharmacokinetics were evaluated using compartmental methods.
Results
Twelve children participated; six (median age 15.2 years; range 9.3–18.6 years) were randomized to receive EPO. All children required dosage increases to 900 IU/kg due to no response. The median (range) apparent EPO AUC0–24 and clearance (CL) were 67.1 IU/ml·hr (13.8–102.6) and 0.26 L/hr/m2 (0.19–1.08), respectively. After the 10th or 11th EPO dose in four of these six EPO patients, the median (range) apparent AUC0–24 and CL of EPO was 126.5 IU/ml·hr (107.3–161.1) and 0.21 L/hr/m2 (0.15–0.25), respectively. No significant correlations were observed between pharmacokinetic parameters and pharmacodynamic effects.
Conclusions
EPO disposition in our patients was similar to other pediatric patient populations or adults receiving IV EPO. Interesting but insignificant trends were noted in pharmacodynamic effects. Pediatr Blood Cancer 2006; 47:572–579. © 2005 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>16317760</pmid><doi>10.1002/pbc.20685</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1545-5009 |
| ispartof | Pediatric blood & cancer, 2006-10, Vol.47 (5), p.572-579 |
| issn | 1545-5009 1545-5017 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68809056 |
| source | Wiley Online Library - AutoHoldings Journals; MEDLINE |
| subjects | Adolescent Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Bone Neoplasms - drug therapy Child Chondrosarcoma - drug therapy Dose-Response Relationship, Drug Double-Blind Method Epoetin Alfa erythropoietin Erythropoietin - pharmacokinetics Erythropoietin - therapeutic use Female General aspects Hematinics - pharmacokinetics Hematinics - therapeutic use Humans Injections, Intravenous Male Medical sciences Melanoma - drug therapy Osteosarcoma - drug therapy pediatrics pharmacodynamics pharmacokinetics Placebos Recombinant Proteins Skin Neoplasms - drug therapy Time Factors Treatment Outcome Tumors |
| title | Pharmacokinetics and pharmacodynamics of intravenous epoetin alfa in children with cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T18%3A48%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pharmacokinetics%20and%20pharmacodynamics%20of%20intravenous%20epoetin%20alfa%20in%20children%20with%20cancer&rft.jtitle=Pediatric%20blood%20&%20cancer&rft.au=Freeman%20III,%20Burgess%20B.&rft.date=2006-10-15&rft.volume=47&rft.issue=5&rft.spage=572&rft.epage=579&rft.pages=572-579&rft.issn=1545-5009&rft.eissn=1545-5017&rft_id=info:doi/10.1002/pbc.20685&rft_dat=%3Cproquest_cross%3E68809056%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=68809056&rft_id=info:pmid/16317760&rfr_iscdi=true |