Three types of recombinant human granulocyte colony-stimulating factor have equivalent biological activities in monkeys.

ABSTRACT

Three types of rhG-CSF are commercially available (non-glycosylated filgrastim, glycosylated lenograstim and N-terminal mutated nartograstim). It has been reported that higher in vitro or in vivo efficacy was found in glycosylated or N-terminal mutated rhG-CSF than in non-glycosylated rhG-CSF. We reported that glycosylated or N-terminal mutated rhG-CSF showed equal efficacy to non-glycosylated rhG-CSF in vivo. In this study, we carried out a direct comparison of pharmacokinetics and pharmacological effects of three rhG-CSFs. We used commercially obtained rhG-CSF products whose activities are guaranteed by the manufacturers. Monkeys have been selected as the experimental animals because of their close relationship to humans concerning drug disposition and daily doses were in accordance with the clinical use of rhG-CSFs. Normal cynomolgus monkeys were given 1.5 or 5 micrograms/kg of rhG-CSF either intravenously or subcutaneously for 5 consecutive days. After intravenous injection, the serum concentration-time profiles of nartograstim were almost identical to those of filgrastim at both doses but the concentrations after lenograstim administration decreased faster. Following subcutaneous administration, no marked differences were observed between the three rhG-CSFs, although lenograstim showed lower serum concentrations than both filgrastim and nartograstim. In spite of some small differences in the pharmacokinetics of the three rhG-CSFs, the pharmacodynamics were identical.