Pharmacokinetic study of a novel recombinant human granulocyte colony-stimulating factor in rats / 中国医学科学杂志(英文版)
Chinese Medical Sciences Journal
;
(4): 13-19, 2010.
Article
in English
| WPRIM
| ID: wpr-299466
ABSTRACT
<p><b>OBJECTIVE</b>To study the pharmacokinetics of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and to determine the proteolytic rates of rhG-CSFa in the whole blood and serum of rats in vitro.</p><p><b>METHODS</b>The pharmacokinetics of rhG-CSFa and conventional (wild type, WT) granulocyte colony-stimulating 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 microg/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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>rhG-CSFa has better serum and whole blood stability in vitro and higher bioavailability in vivo as compared to WT G-CSF.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Reference Standards
/
Blood
/
Recombinant Proteins
/
Enzyme-Linked Immunosorbent Assay
/
Pharmacokinetics
/
Cell Line
/
Granulocyte Colony-Stimulating Factor
/
Sensitivity and Specificity
/
Rats, Sprague-Dawley
/
Genetics
Type of study:
Diagnostic study
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Chinese Medical Sciences Journal
Year:
2010
Type:
Article
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