1991 Volume 6 Issue 6 Pages 887-897
Pharmacokinetics and hematopoietic effects of KW-2228 and recombinant human granulocyte colony stimulating factor (rhG-CSF) in monkeys were studied after a single intravenous, a single subcutaneous and repeated subcutaneous administration at a dose of 10μg/kg or 10μg/kg/day.
1. After a single administration of KW-2228, white blood cell (WBC) count in peripheral blood largely increased. WBC reached a maximum level, about 2 times higher than basal level, at 12hr after administration, and returned to control level at 24hr. WBC count was 4 times higher than basal level, at 12hr after a single subcutaneous administration of KW-2228. After repeated administration for 10 days, the WBC showed 6 times higher level than basal one. It was due to the increase of segmented neutrophils. The same effect was also observed after rhG-CSF administration and there was no differences between the effect of KW-2228 and rhG-CSF. Red blood cell and platelet counts were not changed in this experiments.
2. After a single intravenous administration, KW-2228 and rhG-CSF showed biexponential elimination from the plasma. Half-lives of KW-2228 were 0.43±0.09 (α) and 1.34±0.35hr (β), respectively, which were a little longer than those of rhG-CSF, 0.40±0.04(α) and 1.11±0.05hr (β).
3. After a single subcutaneous administration of KW-2228 or rhG-CSF, both plasma levels reached maximum levels of 13.20±3.76, 8.96±2.81ng/ml respectively, at 2hr, and then were eliminated monoexponentially. Plasma levels of KW-2228 were significantly higher (1.5 ?? 2 times) than those of rhG-CSF, especially in the elimination phase. Elimination half-life of KW-2228 was not different from that of rhG-CSF.
4. After repeated subcutaneous administration for 10 days, Cmax of KW-2228 was decreased to about 2/5 of that of a single administration and elimination half-life was about 2/3. Also AUC was decreased to 1/4. The same results were obtained after rhG-CSF administration.
No difference was shown between plasma levels of KW-2228 and rhG-CSF after repeated administration.
