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Verfasst von:Tillmann, Hanns-Christian [VerfasserIn]   i
 Kuhn, Bernhard [VerfasserIn]   i
 Kränzlin, Bettina [VerfasserIn]   i
 Sadick, Maliha [VerfasserIn]   i
 Gross, J. [VerfasserIn]   i
 Gretz, Norbert [VerfasserIn]   i
 Pill, Johannes [VerfasserIn]   i
Titel:Efficacy and immunogenicity of novel erythropoietic agents and conventional rhEPO in rats with renal insufficiency
Verf.angabe:H.C. Tillmann, B. Kuhn, B. Kränzlin, M. Sadick, J. Gross, N. Gretz and J. Pill
E-Jahr:2006
Jahr:[1 January 2006]
Umfang:8 S.
Illustrationen:Diagramme
Fussnoten:Gesehen am 15.06.2022
Titel Quelle:Enthalten in: Kidney international
Ort Quelle:New York, NY : Elsevier, 1972
Jahr Quelle:2006
Band/Heft Quelle:69(2006), 1 vom: Jan., Seite 60-67
ISSN Quelle:1523-1755
Abstract:Recombinant human erythropoietin (rhEPO) is used to treat anemia in chronic renal insufficiency. Erythropoietin (EPO) immunogenicity can lead to EPO-resistant anemia. Conjugating proteins with polyethylene glycol (PEG) can prolong elimination half-life and diminish protein immunogenicity. We investigated the efficacy of new erythropoietic agents, synthesized by single (Ro 50-3821) and multiple (MIX) integrations of PEG and succinimidyl butanoic acid with rhEPO, in rats with chronic renal insufficiency. Sprague-Dawley rats with surgically induced renal insufficiency received Ro 50-3821 or MIX subcutaneously (s.c.) over 4-12 weeks compared to rhEPO and NaCl. Hemoglobin and antibody levels served as primary efficacy and safety variables. Dosing intervals and dose-response characteristics were investigated. Ro 50-3821 (2.5 μg/kg once weekly) increased hemoglobin levels by 7 g/dl after 4 weeks compared to 1 g/dl in NaCl controls (P<0.05). MIX (2.5 μg/kg once weekly) and rhEPO (0.25 μg/kg three times weekly) increased hemoglobin levels by 3 g/dl. Ro 50-3821 administered for 12 weeks (0.75 μg/kg once weekly) increased hemoglobin levels (from 13 to 19 g/dl) more effectively than rhEPO (0.75 μg/kg once weekly, decline from 13 to 11 g/dl, P<0.05). No antibodies against Ro 50-3821 were detected after 12 weeks of treatment. Antibodies against rhEPO were seen in 69% of animals (P<0.00001). Ro 50-3821 increased hemoglobin levels with once weekly s.c. dosing. Multiple pegylated EPO is less effective. In rats, rhEPO failed to increase hemoglobin levels with once weekly long-term dosing. Antibody formation following rhEPO may explain this finding. Therefore, Ro 50-3821 may provide important clinical advantages compared to unpegylated EPO. It can be administered in longer dosing intervals and has a lower risk of unfavorable immunological responses.
DOI:doi:10.1038/sj.ki.5000006
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1038/sj.ki.5000006
 Volltext: https://www.sciencedirect.com/science/article/pii/S0085253815513057
 DOI: https://doi.org/10.1038/sj.ki.5000006
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:erythropoietin
 long-acting erythropoietic agents
 renal insufficiency
 Ro 50-3821
K10plus-PPN:1807058328
Verknüpfungen:→ Zeitschrift

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