| Online-Ressource |
Verfasst von: | Tillmann, Hanns-Christian [VerfasserIn]  |
| Kuhn, Bernhard [VerfasserIn]  |
| Kränzlin, Bettina [VerfasserIn]  |
| Sadick, Maliha [VerfasserIn]  |
| Gross, J. [VerfasserIn]  |
| Gretz, Norbert [VerfasserIn]  |
| Pill, Johannes [VerfasserIn]  |
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 |
Efficacy and immunogenicity of novel erythropoietic agents and conventional rhEPO in rats with renal insufficiency / Tillmann, Hanns-Christian [VerfasserIn]; [1 January 2006] (Online-Ressource)