1991 Volume 6 Issue 6 Pages 875-885
Pharmacokinetics of Marograstim (KW-2228) was studied in rats. Plasma levels of KW-2228 were measured by the enzyme linked immunosorbent assay (ELISA).
1. After intravenous administration of KW-2228 at doses of 5 ?? 150μg/kg to rats, the KW-2228 was biexponentially eliminated from plasma. However, the elimination half-lifa of KW-2228 that was 0.79hr at dose level of 5μg/kg was prolonged to 2.16hr at 150μg/kg, clearly showing dose-dependency. Then it is thought that the saturable metabolic process might play a role in the disappearance of KW-2228. Plasma levels of KW-2228 were fitted to the compartment model with a Michaelis-Menten type of elimination. The Michaelis constant and maximum elimination rate of KW-2228 in rat were calculated to be 2.3ng/ml and 19.27ng/ml/hr, respectively.
2. After a single subcutaneous administration of KW-2228 to rats, plasma level of KW-2228 reached Cmax at 1.5 ?? 2.Ohr and was mono-exponentially eliminated. The elimination half-lives of KW-2228 were about 1.5hr at 50 and 150μg/kg. Non-linearities of Cmax and AUC versus doses were recognized.
3. After repeated subcutaneous administration of KW-2228 at 50μg/kg/day for 10 days, plasma levels of KW-2228 at 6hr after last administration and elimination half-lives were significantly lower than that of the single administration.
4. Pharmacokinetics of rhG-CSF after intravenous or subcutaneous administration at 50μg/kg was almost equal to that of KW-2228.
