3 TYPES OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR HAVE EQUIVALENT BIOLOGICAL-ACTIVITIES IN MONKEYS

Three types of rhG-CSF are commercially available (non-glycosylated: f ilgrastim, glycosylated: lenograstim and N-terminal mutated: nartogras tim). It has been reported that higher in vitro or in vivo efficacy wa s found in glycosylated or ill-terminal mutated rhG-CSF than in non-gl ycosylated rhG-CSF. We reported that glycosylated or N-terminal mutate d rhG-CSF showed equal efficacy to non-glycosylated rhG-CSF in vivo. I n this study, we carried out a direct comparison of pharmacokinetics a nd pharmacological effects of three rhG-CSFs. We used commercially obt ained rhG-CSF products whose activities are guaranteed by the manufact urers, 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. Norm al cynomolgus monkeys were given 1.5 or 5 mu g/kg of rhG-CSF either in travenously or subcutaneously for 5 consecutive days. After intravenou s injection, the serum concentration-time profiles of nartograstim wer e almost identical to those of filgrastim at both doses but the concen trations after lenograstim administration decreased faster, Following subcutaneous administration, no marked differences were observed betwe en the three rhG-CSFs, although lenograstim showed lower serum concent rations than both filgrastim and nartograstim, In spite of some small differences in the pharmacokinetics of the three rhG-CSFs, the pharmac odynamics were identical. (C) 1997 Academic Press Limited.