Pharmacokinetics of recombinant human granulocyte colony-stimulating factor in rabbits and mice
Abstract
AIM: To study the pharmacokinetics of recombinant human granulocyte
colony-stimulating factor (rhGCSF) in rabbits and mice.
METHODS: 125I-rhGCSF was prepared by iodogen method and determined by size
exclusive HPLC (SEHPLC).
RESULTS: Concentration-time curves after i.v. 125I-rhGCSF in rabbits were best
fitted with 2-compartment open model. The alpha and terminal elimination T1/2
were 0.25-0.33 and 3.2-4.6 h, respectively. AUC increased with doses, and Cls and
K10 were similar. Tpeak was 0.59 +/- 0.25 h after s.c., and elimination T1/2 was
similar to that after i.v. The bioavailability after sc was 1.0. In mice the
highest level was found in renal system, the next was bile-enteric system. Levels
in lymph nodes, bone marrow, and spleen were approximately equal to or slightly
lower than that in plasma, while the levels in brain, fat, and muscles were the
lowest. About 68%-86% were recovered in urine and feces.
CONCLUSION: Pharamcokinetics of 125I-rhGCSF in rabbits and mice provided a useful
index for clinical trial.
Keywords:
colony-stimulating factor (rhGCSF) in rabbits and mice.
METHODS: 125I-rhGCSF was prepared by iodogen method and determined by size
exclusive HPLC (SEHPLC).
RESULTS: Concentration-time curves after i.v. 125I-rhGCSF in rabbits were best
fitted with 2-compartment open model. The alpha and terminal elimination T1/2
were 0.25-0.33 and 3.2-4.6 h, respectively. AUC increased with doses, and Cls and
K10 were similar. Tpeak was 0.59 +/- 0.25 h after s.c., and elimination T1/2 was
similar to that after i.v. The bioavailability after sc was 1.0. In mice the
highest level was found in renal system, the next was bile-enteric system. Levels
in lymph nodes, bone marrow, and spleen were approximately equal to or slightly
lower than that in plasma, while the levels in brain, fat, and muscles were the
lowest. About 68%-86% were recovered in urine and feces.
CONCLUSION: Pharamcokinetics of 125I-rhGCSF in rabbits and mice provided a useful
index for clinical trial.