Chinese Medical Sciences Journal ›› 2010, Vol. 25 ›› Issue (1): 13-19.doi: 10.1016/S1001-9294(10)60014-4

• Original Article • Previous Articles     Next Articles

Pharmacokinetic Study of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

Xiao-xiao Liu1 and Yong-ping Jiang1; 2   

  1. 1Biopharmaceutical R&D Center; Chinese Academy of Medical Sciences & Peking Union Medical College; Suzhou 215126; China 2Biopharmagen Corp.; Suzhou 215126; China 2Biopharmagen Corp.; Suzhou 215126; China
  • Online:2010-03-10 Published:2010-03-10
  • Supported by:

    Supported by State Scientific Key Projects for New Drug Research and Development (2009ZX09102-250);; High-tech Research Project for Medicine and Pharmacology of Jiangsu province (BG20070605)

Abstract: Objective To study the pharmacokinetics of a novel recombinant human granulocyte colonystimulating factor (rhG-CSFa) in rats and to determine the proteolytic rates of rhG-CSFa in the whole blood and serum of rats in vitro. Methods The pharmacokinetics of rhG-CSFa and conventional (wild type,WT) granulocyte colonystimulating factor (G-CSF) were investigated in Sprague-Dawley rats which received either intravenous or subcutaneous injection of rhG-CSFa or WT G-CSF at three different doses (20,50,or 100 μg/kg). The blood samples of rats were collected at multiple time points (from 0.08 to 12 h) and the concentrations of rhG-CSFa and WT G-CSF in serum were determined with a sandwich enzyme-linked immunosorbent assay (ELISA). For the study of proteolytic rates in vitro,the concentrations of rhG-CSFa or WT G-CSF were determined at 3-minute intervals after addition of the respective drug to rat’s whole blood or serum. Results Pharmacokinetic analysis of serum rhG-CSFa or WT G-CSF levels indicated that,at each dose tested,for either route of drug administration,the area under concentration-time curve values and the maximum serum concentration of rhG-CSFa were higher than those of WT G-CSF,and the serum half life of rhG-CSFa was longer than that of WT G-CSF. Subsequent in vitro whole blood and serum stability study showed that the rates of drug degradation in WT G-CSF were 1.8 folds and 1.5 folds higher than those in rhG-CSFa,respectively. Conclusion rhG-CSFa has better serum and whole blood stability in vitro and higher bioavailability in vivo as compared to WT G-CSF.

Key words: recombinant human granulocyte colony-stimulating factor, pharmacokinetics, half life, bioavailability, proteolytic rate

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