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 v...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.展开更多
Two different salts of diclofenac,diclofenac sodium and diclofenac potassium,in tablet dosage form were tested for their bioavailability and disposition kinetics in a group of eighteen rabbits in normal and experiment...Two different salts of diclofenac,diclofenac sodium and diclofenac potassium,in tablet dosage form were tested for their bioavailability and disposition kinetics in a group of eighteen rabbits in normal and experimentally induced dehydrated conditions with a wash out period of 7 days between both stages of study.Biochemical and physiological parameters were also measured in both normal and dehydrated states.Diclofenac levels in plasma were determined using a validated reversed phase HPLC method.Primary kinetic parameters i.e.AUC0-∞,Cmax,Tmax and other disposition kinetics were obtained with non-compartmental procedure.Biochemical parameters i.e.packed cell volume,plasma glucose and total lipid concentration in dehydrated rabbits increased significantly.Plasma concentration of diclofenac sodium and diclofenac potassium decreased significantly in water deprived rabbits.In comparison,diclofenac potassium in normal and dehydrated state of the same group of rabbits showed a significantly increased plasma concentration when compared with diclofenac sodium.展开更多
基金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)
文摘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.
文摘Two different salts of diclofenac,diclofenac sodium and diclofenac potassium,in tablet dosage form were tested for their bioavailability and disposition kinetics in a group of eighteen rabbits in normal and experimentally induced dehydrated conditions with a wash out period of 7 days between both stages of study.Biochemical and physiological parameters were also measured in both normal and dehydrated states.Diclofenac levels in plasma were determined using a validated reversed phase HPLC method.Primary kinetic parameters i.e.AUC0-∞,Cmax,Tmax and other disposition kinetics were obtained with non-compartmental procedure.Biochemical parameters i.e.packed cell volume,plasma glucose and total lipid concentration in dehydrated rabbits increased significantly.Plasma concentration of diclofenac sodium and diclofenac potassium decreased significantly in water deprived rabbits.In comparison,diclofenac potassium in normal and dehydrated state of the same group of rabbits showed a significantly increased plasma concentration when compared with diclofenac sodium.
