Pharmacokinetics and Pharmacodynamics of Recombinant Human EPO-Fc Fusion Protein In Vivo
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| Authors: | Xunlong Shi Jianjun Yang Haiyan Zhu Li Ye Meiqing Feng Jiyang Li Hai Huang Qun Tao Dan Ye Lee-Hwei K Sun Bill N C Sun Cecily R Y Sun Guizhen Han Yuanyuan Liu Minghui Yao Pei Zhou Dianwen Ju |
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| Institution: | 1. Department of Biosynthesis, School of
Pharmacy, Fudan University, Shanghai, China.; 2. Shanghai Meiye Biotech Institute, Shanghai,
China.; 3. PharMab (Shanghai), Inc., Shanghai,
China.; 4. Department of Pharmacology, School of
Medicine, Fudan University, Shanghai, China.; IIT Research Institute, United States of
America, |
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| 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. |
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