PHARMACOKINETICS OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR IN RABBITS AND MICE

To study the pharmacokinetics of recombinant human granulocyte colony- stimulating factor (rhGCSF) in rabbits and mice. METHODS: I-125-rhGCSF was prepared by iodogen method and determined by size exclusive HPLC (SEHPLC). RESULTS: Concentration-time curves after iv I-125-rhGCSF in rabbits were best fitted with 2-compartment open model. The a and term inal elimination T 1/2 were 0.25 - 0.33 and 3.2 - 4.6 h, respectively. AUC increased with doses, and Cl-s and K-10 were similar. T-peak was 0.59 +/- 0.25 h after sc, and elimination T 1/2 was similar to that af ter iv. The bioavailability after sc was 1.0. In mice the highest leve l 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, a nd muscles were the lowest. About 68 %-86 % were recovered in urine an d feces. CONCLUSION: Pharamcokinetics of I-125-rhGCSF in rabbits and m ice provided a useful index for clinical trial.