Erythropoiesis stimulating agents: approaches to modulate activity

被引:37
|
作者
Sinclair, Angus M. [1 ]
机构
[1] Amgen Inc, 1 Amgen Ctr Dr, Thousand Oaks, CA 91320 USA
来源
BIOLOGICS-TARGETS & THERAPY | 2013年 / 7卷
关键词
darbepoetin alfa; erythropoiesis; erythropoietin; glycosylation; pharmacokinetics; pharmacology; polyethylene glycols;
D O I
10.2147/BTT.S45971
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 pharma-cokinetic 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.
引用
收藏
页码:161 / 174
页数:14
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