Pharmacokinetics and pharmacodynamics of recombinant human EPO-Fc fusion protein in vivo

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...

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Published in:	PloS one Vol. 8; no. 8; p. e72673
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 19-08-2013 Public Library of Science (PLoS)
Subjects:	Ablation (Surgery) Analysis Anemia Anemia - drug therapy Animal models Animals Biology Biosynthesis Blood Cancer therapies Chemotherapy Clinical trials Cyclophosphamide Cytokines Drug dosages Engineering Erythropoietin Erythropoietin - administration & dosage Erythropoietin - pharmacokinetics Erythropoietin - pharmacology Erythropoietin - therapeutic use Fc receptors Fusion protein Glycosylated hemoglobin Health aspects Hematocrit Hemoglobin Humans In vivo methods and tests Irradiation Kidney - drug effects Kidney - pathology Kidneys Macaca mulatta - physiology Medical research Medicine Mice, Inbred C57BL Molecular weight Monkeys Pharmacodynamics Pharmacokinetics Pharmacology Pharmacy Proteins Radiation Rats Rats, Sprague-Dawley Recombinant Fusion Proteins - administration & dosage Recombinant Fusion Proteins - pharmacokinetics Recombinant Fusion Proteins - pharmacology Recombinant Fusion Proteins - therapeutic use Rodents Veterinary Science Whole-Body Irradiation China
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Summary:	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.
Bibliography:	Competing Interests: QT, DY, DJ are founders and JY is an employee of Meiyer Biotech Institute, and LHKS, BNCS, CRYS are founders of PharMab, Inc. This affiliation, however, does not in anyway alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. The other authors report no conflict of interest. Conceived and designed the experiments: QT DY BNCS MY DJ. Performed the experiments: XS JY HZ JL HH LY MF GH YL. Analyzed the data: LHKS CRYS YL MY PZ. Wrote the paper: XS PZ DJ.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0072673