title: 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.
authors: Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai, China.
authors: Xunlong
authors: X
authors: Shi
authors: Jianjun
authors: J
authors: Yang
authors: Haiyan
authors: H
authors: Zhu
authors: Li
authors: L
authors: Ye
authors: Meiqing
authors: M
authors: Feng
authors: Jiyang
authors: J
authors: Li
authors: Hai
authors: H
authors: Huang
authors: Qun
authors: Q
authors: Tao
authors: Dan
authors: D
authors: Ye
authors: Lee-Hwei K
authors: LH
authors: Sun
authors: Bill N C
authors: BN
authors: Sun
authors: Cecily R Y
authors: CR
authors: Sun
authors: Guizhen
authors: G
authors: Han
authors: Yuanyuan
authors: Y
authors: Liu
authors: Minghui
authors: M
authors: Yao
authors: Pei
authors: P
authors: Zhou
authors: Dianwen
authors: D
authors: Ju
mesh_terms: D000740:Anemia / Q000188:drug therapy; D000818:Animals; D003520:Cyclophosphamide; D004921:Erythropoietin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008253:Macaca mulatta / Q000502:physiology*; D008810:Mice, Inbred C57BL; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D014916:Whole-Body Irradiation
chemical_list: D011993:Recombinant Fusion Proteins; D004921:Erythropoietin; D003520:Cyclophosphamide
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