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

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.

DOI: 10.1371/journal.pone.0072673

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@inproceedings{Shi2013PharmacokineticsAP, title={Pharmacokinetics and Pharmacodynamics of Recombinant Human EPO-Fc Fusion Protein In Vivo}, author={Xunlong Shi and Jianjun Yang and Haiyan Zhu and Li Ye and Mei-qing Feng and Jiyang Li and Hai Huang and Qun Tao and Dan Ye and Lee-Hwei K. Sun and Bill N. C. Sun and Cecily R. Y. Sun and Guizhen Han and Yuanyuan Liu and Minghui Yao and Pei Zhou and Dianwen Ju}, booktitle={PloS one}, year={2013} }