Disposition of Marograstim (KW-2228) (5) : Correlation between bioassay and ELISA in measurement for plasma concentration of KW-2228 after intravenous or subcutaneous administration of KW-2228

Marograstim (KW-2228) is a derivative of human granulocyte colony-stimulating factor(rhG-CSF). In order to determine biological activity of KW-2228 in the plasma, a bioassay method of G-CSF was developed. Determination limit of the bioassay was 2ng/ml for plasma samples. A comparison of plasma concentrations, determined by the bioassay and the enzyme-linked imm unosorbent assay using specific anti KW-2228 antibody (ELISA), was performed on samples after intravenous or subcutaneous administration of KW-2228 to human volunteers (2μg/kg), monkeys (10μg/kg), rats (50μg/kg) and mice (50μg/kg). In all species, there was no difference between the plasma concentrations of KW-2228 determined by the bioassay and ELISA. There was a significant correlation between plasma concentrations of KW-2228 determined by the bioassay and ELISA (p<0.01). This result suggests that ELISA is a specific method to measure only the drug retaining biological activity of GCSF. Therefore the ELISA is thought to be a very useful method for pharmacokinetic and pharmacodynamic studies. Plasma concentration of KW-2228 measured by the bioassay showed slower elimination after subcutaneous administration than after intravenous administration. The route of subcutaneous administration is the better method for maintenance of plasma concentration. Based on the pharmacokinetic parameters of KW-2228 after intravenous and subcutaneous administration there was no species difference in drug disposition.