TITLE

Pharmacokinetics and Pharmacodynamics of Recombinant Human EPO-Fc Fusion Protein In Vivo

AUTHOR(S)
Shi, Xunlong; Yang, Jianjun; Zhu, Haiyan; Ye, Li; Feng, Meiqing; Li, Jiyang; Huang, Hai; Tao, Qun; Ye, Dan; Sun, Lee-Hwei K.; Sun, Bill N. C.; Sun, Cecily R. Y.; Han, Guizhen; Liu, Yuanyuan; Yao, Minghui; Zhou, Pei; Ju, Dianwen
PUB. DATE
August 2013
SOURCE
PLoS ONE;Aug2013, Vol. 8 Issue 8, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
In this study, the in vivo pharmacokinetics and pharmacodynamics of a novel recombinant human erythropoietin (rhEPO) Fc fusion protein, rhEPO-Fc, were studied in both rodents and rhesus monkeys. Animal models of anemia induced by irradiation, cyclophosphamide and partial renal ablation were used to evaluate therapeutic effects of rhEPO-Fc. We have demonstrated that serum half-life of rhEPO-Fc was 29.5 to 38.9 h at doses of 8, 25, 80 µg/kg in rhesus monkeys and 35.5 to 43.5 h at doses of 16, 50, 160 µg/kg in rats. In anemia animal models, rhEPO-Fc dose-dependently (7.5–30.0 µg/kg in mice, 5.4–21.4 µg/kg in rats and 5.0–10.0 µg/kg in rhesus monkeys) increased reticulocyte level, followed by an increase of RBC count, hemoglobin and hematocrit levels. At reduced intervention frequency of weekly treatments, rhEPO-Fc showed similar hematopoietic effects as compared with rhEPO given three times a week. These results indicated that rhEPO-Fc could potentially be used in treatment of anemia and warrants future clinical trials.
ACCESSION #
90072497

 

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