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Erythropoiesis stimulating agents approaches to modulate activity

Authors Sinclair AM

Received 30 March 2013

Accepted for publication 14 May 2013

Published 3 July 2013 Volume 2013:7 Pages 161—174

DOI https://doi.org/10.2147/BTT.S45971

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Angus M Sinclair

Amgen Inc, Thousand Oaks, CA, USA

Abstract: Recombinant human erythropoietin (rHuEPO), such as the approved agents epoetin alfa and epoetin beta, has been used successfully for over 20 years to treat anemia in millions of patients. However, due to the relatively short half-life of the molecule (approximately 8 hours), frequent dosing may be required to achieve required hemoglobin levels. Therefore, a need was identified in some anemic patient populations for erythropoiesis stimulating agents with longer half-lives that required less frequent dosing. This need led to the development of second generation molecules which are modified versions of rHuEPO with improved pharmacokinetic and pharmacodynamic properties such as darbepoetin alfa, a hyperglycosylated analog of rHuEPO, and pegzyrepoetin, a pegylated rHuEPO. Third generation molecules, such as peginesatide, which are peptide mimetics that have no sequence homology to rHuEPO have also recently been developed. The various molecular, pharmacokinetic, and pharmacodynamic properties of these and other erythropoiesis stimulating agents will be discussed in this review.

Keywords: darbepoetin alfa, erythropoiesis, erythropoietin, glycosylation, pharmacokinetics, pharmacology, polyethylene glycols

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