DOSE-DEPENDENT PHARMACOKINETICS OF HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN RABBITS

The pharmacokinetic parameters of HGM-CSF, such as t1/2 (11.3, 10.4, 3 9.2, 39.2 vs 51.6 min), MRT (11.6, 10,9, 22.9, 20.3 vs 18.3 min), CL(2 5.0,21.1, 6.98,7.94 vs 6.51 ml min-1 kg-1), CL(NR) (24.6, 19.9, 6.87, 6.92 vs 4.24 ml min-1 kg-1) and V(ss) (292, 211, 162, 162 vs 120 ml kg -1) were dose-dependent after intravenous administration of the factor to rabbits at the doses of 0.05, 0.1, 0.5, 1.0 and 2.5 mg kg-1, respe ctively. The dose-dependent pharmacokinetics of HGM-CSF in rabbits app eared to represent saturable metabolism of the factor at the dose rang es studied. HGM-CSF was highly concentrated in the kidney and liver, a nd less concentrated in other tissues or organs studied at 2 h after s ubcutaneous administration of the factor, 0.5 mg kg-1 to rabbits.