Pharmacokinetics and pharmacodynamics of darbepoetin alfa and epoetin in patients undergoing dialysis
Objective The aim of this multicenter, randomized, open‐label study was to compare the pharmacokinetic and pharmacodynamic profiles of darbepoetin alfa, a new erythropoiesis‐stimulating protein, and recombinant human erythropoietin (epoetin) after repeated intravenous dosing in patients with chronic...
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| Veröffentlicht in: | Clinical pharmacology and therapeutics 2002-11, Vol.72 (5), p.546-555 |
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| creator | Allon, Michael Kleinman, Kenneth Walczyk, Michael Kaupke, Charles Messer‐Mann, Louise Olson, Kurt Heatherington, Anne C. Maroni, Bradley J. |
| description | Objective
The aim of this multicenter, randomized, open‐label study was to compare the pharmacokinetic and pharmacodynamic profiles of darbepoetin alfa, a new erythropoiesis‐stimulating protein, and recombinant human erythropoietin (epoetin) after repeated intravenous dosing in patients with chronic kidney disease receiving hemodialysis.
Methods
Forty‐seven patients were randomized to receive darbepoetin alfa administered once weekly (n = 17) or 3 times weekly (n = 15) or epoetin administered 3 times weekly (n = 15) for up to 52 weeks. Pharmacokinetic profiles were measured during weeks 1 and 12 and at hemoglobin steady state (defined as a hemoglobin concentration within the target range for 4 consecutive weeks after week 12 with no change in study drug dose) or between weeks 36 and 40, whichever occurred first.
Results
At each of the 3 time points evaluated, the terminal half‐life of darbepoetin alfa was 2 to 3 times longer and the clearance approximately 4 times slower than those of epoetin. At week 12, the terminal half‐life was 23.4 hours with darbepoetin alfa once weekly, 18.3 hours with darbepoetin alfa 3 times weekly, and 8.0 hours with epoetin 3 times weekly. The pharmacokinetics of darbepoetin alfa was not dependent on dose or time. Mean hemoglobin values at steady state were all approximately 11 g/dL, within the target range of 9.0 to 13.0 g/dL. Safety analyses revealed no differences between darbepoetin alfa and epoetin.
Conclusions
The pharmacokinetic and pharmacodynamic profiles and safety data for darbepoetin alfa demonstrate that it can be administered less frequently than epoetin in patients with chronic kidney disease receiving hemodialysis, thus simplifying anemia management.
Clinical Pharmacology & Therapeutics (2002) 72, 546–555; doi: 10.1067/mcp.2002.128374 |
| doi_str_mv | 10.1067/mcp.2002.128374 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72661423</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72661423</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4416-5525ee00e9630f598d5a20e46280e697d1fb89b0abef7de01c583684b29333c13</originalsourceid><addsrcrecordid>eNqFkE1rGzEQhkVpqB2n597KXtrb2vpeLTkF06YBQ3xwzkIrzbpqd7UbySb430euN-RYGBjm5ZkZeBD6QvCSYFmtejsuKcZ0SahiFf-A5kQwWkrBxEc0xxjXZU2ZnKHrlP7kkddKfUIzQjmVgqg5gu1vE3tjh78-wMHbVJjginEK3SmY_hwObeFMbGAcMhQK07XmH_gW5BrNwUM4pOIYHMT94MO-cN50p-TTDbpqTZfg89QX6Onnj936V7l5vH9Y321KyzmRpRBUAGAMtWS4FbVywlAMXFKFQdaVI22j6gabBtrKASZWKCYVb2jNGLOELdD3y90xDs9HSAfd-2Sh60yA4Zh0RaUknLIMri6gjUNKEVo9Rt-beNIE67NZnc3qs1l9MZs3vk6nj00P7p2fVGbg2wSYZLOgaIL16Z3jmGX9VeZuL9yL7-D0v796vd2tN9vdOSJEsldHtZQC</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>72661423</pqid></control><display><type>article</type><title>Pharmacokinetics and pharmacodynamics of darbepoetin alfa and epoetin in patients undergoing dialysis</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Allon, Michael ; Kleinman, Kenneth ; Walczyk, Michael ; Kaupke, Charles ; Messer‐Mann, Louise ; Olson, Kurt ; Heatherington, Anne C. ; Maroni, Bradley J.</creator><creatorcontrib>Allon, Michael ; Kleinman, Kenneth ; Walczyk, Michael ; Kaupke, Charles ; Messer‐Mann, Louise ; Olson, Kurt ; Heatherington, Anne C. ; Maroni, Bradley J.</creatorcontrib><description>Objective
The aim of this multicenter, randomized, open‐label study was to compare the pharmacokinetic and pharmacodynamic profiles of darbepoetin alfa, a new erythropoiesis‐stimulating protein, and recombinant human erythropoietin (epoetin) after repeated intravenous dosing in patients with chronic kidney disease receiving hemodialysis.
Methods
Forty‐seven patients were randomized to receive darbepoetin alfa administered once weekly (n = 17) or 3 times weekly (n = 15) or epoetin administered 3 times weekly (n = 15) for up to 52 weeks. Pharmacokinetic profiles were measured during weeks 1 and 12 and at hemoglobin steady state (defined as a hemoglobin concentration within the target range for 4 consecutive weeks after week 12 with no change in study drug dose) or between weeks 36 and 40, whichever occurred first.
Results
At each of the 3 time points evaluated, the terminal half‐life of darbepoetin alfa was 2 to 3 times longer and the clearance approximately 4 times slower than those of epoetin. At week 12, the terminal half‐life was 23.4 hours with darbepoetin alfa once weekly, 18.3 hours with darbepoetin alfa 3 times weekly, and 8.0 hours with epoetin 3 times weekly. The pharmacokinetics of darbepoetin alfa was not dependent on dose or time. Mean hemoglobin values at steady state were all approximately 11 g/dL, within the target range of 9.0 to 13.0 g/dL. Safety analyses revealed no differences between darbepoetin alfa and epoetin.
Conclusions
The pharmacokinetic and pharmacodynamic profiles and safety data for darbepoetin alfa demonstrate that it can be administered less frequently than epoetin in patients with chronic kidney disease receiving hemodialysis, thus simplifying anemia management.
Clinical Pharmacology & Therapeutics (2002) 72, 546–555; doi: 10.1067/mcp.2002.128374</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1067/mcp.2002.128374</identifier><identifier>PMID: 12426518</identifier><identifier>CODEN: CLPTAT</identifier><language>eng</language><publisher>New York, NY: Nature Publishing</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Darbepoetin alfa ; Epoetin Alfa ; Erythropoietin - adverse effects ; Erythropoietin - analogs & derivatives ; Erythropoietin - pharmacokinetics ; Erythropoietin - pharmacology ; Female ; Half-Life ; Hemoglobins - analysis ; Humans ; Male ; Medical sciences ; Middle Aged ; Models, Biological ; Pharmacology. Drug treatments ; Recombinant Proteins ; Renal Dialysis</subject><ispartof>Clinical pharmacology and therapeutics, 2002-11, Vol.72 (5), p.546-555</ispartof><rights>2002 American Society for Clinical Pharmacology and Therapeutics</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4416-5525ee00e9630f598d5a20e46280e697d1fb89b0abef7de01c583684b29333c13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1067%2Fmcp.2002.128374$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1067%2Fmcp.2002.128374$$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=14030497$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12426518$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Allon, Michael</creatorcontrib><creatorcontrib>Kleinman, Kenneth</creatorcontrib><creatorcontrib>Walczyk, Michael</creatorcontrib><creatorcontrib>Kaupke, Charles</creatorcontrib><creatorcontrib>Messer‐Mann, Louise</creatorcontrib><creatorcontrib>Olson, Kurt</creatorcontrib><creatorcontrib>Heatherington, Anne C.</creatorcontrib><creatorcontrib>Maroni, Bradley J.</creatorcontrib><title>Pharmacokinetics and pharmacodynamics of darbepoetin alfa and epoetin in patients undergoing dialysis</title><title>Clinical pharmacology and therapeutics</title><addtitle>Clin Pharmacol Ther</addtitle><description>Objective
The aim of this multicenter, randomized, open‐label study was to compare the pharmacokinetic and pharmacodynamic profiles of darbepoetin alfa, a new erythropoiesis‐stimulating protein, and recombinant human erythropoietin (epoetin) after repeated intravenous dosing in patients with chronic kidney disease receiving hemodialysis.
Methods
Forty‐seven patients were randomized to receive darbepoetin alfa administered once weekly (n = 17) or 3 times weekly (n = 15) or epoetin administered 3 times weekly (n = 15) for up to 52 weeks. Pharmacokinetic profiles were measured during weeks 1 and 12 and at hemoglobin steady state (defined as a hemoglobin concentration within the target range for 4 consecutive weeks after week 12 with no change in study drug dose) or between weeks 36 and 40, whichever occurred first.
Results
At each of the 3 time points evaluated, the terminal half‐life of darbepoetin alfa was 2 to 3 times longer and the clearance approximately 4 times slower than those of epoetin. At week 12, the terminal half‐life was 23.4 hours with darbepoetin alfa once weekly, 18.3 hours with darbepoetin alfa 3 times weekly, and 8.0 hours with epoetin 3 times weekly. The pharmacokinetics of darbepoetin alfa was not dependent on dose or time. Mean hemoglobin values at steady state were all approximately 11 g/dL, within the target range of 9.0 to 13.0 g/dL. Safety analyses revealed no differences between darbepoetin alfa and epoetin.
Conclusions
The pharmacokinetic and pharmacodynamic profiles and safety data for darbepoetin alfa demonstrate that it can be administered less frequently than epoetin in patients with chronic kidney disease receiving hemodialysis, thus simplifying anemia management.
Clinical Pharmacology & Therapeutics (2002) 72, 546–555; doi: 10.1067/mcp.2002.128374</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Darbepoetin alfa</subject><subject>Epoetin Alfa</subject><subject>Erythropoietin - adverse effects</subject><subject>Erythropoietin - analogs & derivatives</subject><subject>Erythropoietin - pharmacokinetics</subject><subject>Erythropoietin - pharmacology</subject><subject>Female</subject><subject>Half-Life</subject><subject>Hemoglobins - analysis</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Models, Biological</subject><subject>Pharmacology. Drug treatments</subject><subject>Recombinant Proteins</subject><subject>Renal Dialysis</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1rGzEQhkVpqB2n597KXtrb2vpeLTkF06YBQ3xwzkIrzbpqd7UbySb430euN-RYGBjm5ZkZeBD6QvCSYFmtejsuKcZ0SahiFf-A5kQwWkrBxEc0xxjXZU2ZnKHrlP7kkddKfUIzQjmVgqg5gu1vE3tjh78-wMHbVJjginEK3SmY_hwObeFMbGAcMhQK07XmH_gW5BrNwUM4pOIYHMT94MO-cN50p-TTDbpqTZfg89QX6Onnj936V7l5vH9Y321KyzmRpRBUAGAMtWS4FbVywlAMXFKFQdaVI22j6gabBtrKASZWKCYVb2jNGLOELdD3y90xDs9HSAfd-2Sh60yA4Zh0RaUknLIMri6gjUNKEVo9Rt-beNIE67NZnc3qs1l9MZs3vk6nj00P7p2fVGbg2wSYZLOgaIL16Z3jmGX9VeZuL9yL7-D0v796vd2tN9vdOSJEsldHtZQC</recordid><startdate>200211</startdate><enddate>200211</enddate><creator>Allon, Michael</creator><creator>Kleinman, Kenneth</creator><creator>Walczyk, Michael</creator><creator>Kaupke, Charles</creator><creator>Messer‐Mann, Louise</creator><creator>Olson, Kurt</creator><creator>Heatherington, Anne C.</creator><creator>Maroni, Bradley J.</creator><general>Nature Publishing</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>200211</creationdate><title>Pharmacokinetics and pharmacodynamics of darbepoetin alfa and epoetin in patients undergoing dialysis</title><author>Allon, Michael ; Kleinman, Kenneth ; Walczyk, Michael ; Kaupke, Charles ; Messer‐Mann, Louise ; Olson, Kurt ; Heatherington, Anne C. ; Maroni, Bradley J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4416-5525ee00e9630f598d5a20e46280e697d1fb89b0abef7de01c583684b29333c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Darbepoetin alfa</topic><topic>Epoetin Alfa</topic><topic>Erythropoietin - adverse effects</topic><topic>Erythropoietin - analogs & derivatives</topic><topic>Erythropoietin - pharmacokinetics</topic><topic>Erythropoietin - pharmacology</topic><topic>Female</topic><topic>Half-Life</topic><topic>Hemoglobins - analysis</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Models, Biological</topic><topic>Pharmacology. Drug treatments</topic><topic>Recombinant Proteins</topic><topic>Renal Dialysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Allon, Michael</creatorcontrib><creatorcontrib>Kleinman, Kenneth</creatorcontrib><creatorcontrib>Walczyk, Michael</creatorcontrib><creatorcontrib>Kaupke, Charles</creatorcontrib><creatorcontrib>Messer‐Mann, Louise</creatorcontrib><creatorcontrib>Olson, Kurt</creatorcontrib><creatorcontrib>Heatherington, Anne C.</creatorcontrib><creatorcontrib>Maroni, Bradley J.</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>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Allon, Michael</au><au>Kleinman, Kenneth</au><au>Walczyk, Michael</au><au>Kaupke, Charles</au><au>Messer‐Mann, Louise</au><au>Olson, Kurt</au><au>Heatherington, Anne C.</au><au>Maroni, Bradley J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics and pharmacodynamics of darbepoetin alfa and epoetin in patients undergoing dialysis</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin Pharmacol Ther</addtitle><date>2002-11</date><risdate>2002</risdate><volume>72</volume><issue>5</issue><spage>546</spage><epage>555</epage><pages>546-555</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><coden>CLPTAT</coden><abstract>Objective
The aim of this multicenter, randomized, open‐label study was to compare the pharmacokinetic and pharmacodynamic profiles of darbepoetin alfa, a new erythropoiesis‐stimulating protein, and recombinant human erythropoietin (epoetin) after repeated intravenous dosing in patients with chronic kidney disease receiving hemodialysis.
Methods
Forty‐seven patients were randomized to receive darbepoetin alfa administered once weekly (n = 17) or 3 times weekly (n = 15) or epoetin administered 3 times weekly (n = 15) for up to 52 weeks. Pharmacokinetic profiles were measured during weeks 1 and 12 and at hemoglobin steady state (defined as a hemoglobin concentration within the target range for 4 consecutive weeks after week 12 with no change in study drug dose) or between weeks 36 and 40, whichever occurred first.
Results
At each of the 3 time points evaluated, the terminal half‐life of darbepoetin alfa was 2 to 3 times longer and the clearance approximately 4 times slower than those of epoetin. At week 12, the terminal half‐life was 23.4 hours with darbepoetin alfa once weekly, 18.3 hours with darbepoetin alfa 3 times weekly, and 8.0 hours with epoetin 3 times weekly. The pharmacokinetics of darbepoetin alfa was not dependent on dose or time. Mean hemoglobin values at steady state were all approximately 11 g/dL, within the target range of 9.0 to 13.0 g/dL. Safety analyses revealed no differences between darbepoetin alfa and epoetin.
Conclusions
The pharmacokinetic and pharmacodynamic profiles and safety data for darbepoetin alfa demonstrate that it can be administered less frequently than epoetin in patients with chronic kidney disease receiving hemodialysis, thus simplifying anemia management.
Clinical Pharmacology & Therapeutics (2002) 72, 546–555; doi: 10.1067/mcp.2002.128374</abstract><cop>New York, NY</cop><pub>Nature Publishing</pub><pmid>12426518</pmid><doi>10.1067/mcp.2002.128374</doi><tpages>10</tpages></addata></record> |
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| subjects | Adult Aged Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Darbepoetin alfa Epoetin Alfa Erythropoietin - adverse effects Erythropoietin - analogs & derivatives Erythropoietin - pharmacokinetics Erythropoietin - pharmacology Female Half-Life Hemoglobins - analysis Humans Male Medical sciences Middle Aged Models, Biological Pharmacology. Drug treatments Recombinant Proteins Renal Dialysis |
| title | Pharmacokinetics and pharmacodynamics of darbepoetin alfa and epoetin in patients undergoing dialysis |
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