THE EFFECTS OF DOSE AND ROUTE OF ADMINISTRATION ON THE PHARMACOKINETICS OF GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR

The pharmacokinetics of granulocyte-macrophage colony stimulating factor (GM-CSF) (0.3-30-mu-g/kg) were studied after subcutaneous bolus (n = 16) or intravenous bolus (n = 5) injection or 2 h intravenous infusion (n = 12). Each method of administration gave a different GM-CSF concentration-time profile. Highest peak serum concentrations (C(max)) followed the intravenous bolus, and the time GM-CSF persisted at a concentration greater than 1 ng/ml (t > 1 ng/ml) was longer after a subcutaneous than after an intravenous injection. Area under the concentration-time curve (AUC), C(max)) and t > 1 ng/ml all increased with dose for each method of administration. After intravenous administration, there was a two-phase decline in concentration. The half-life (t 1/2) of the terminal phase following an intravenous bolus ranged from 0.24 to 1.18 h and, following intravenous infusion, from 0.62 to 9.07 h and appeared to increase with dose. The apparent clearance was greatest following subcutaneous injection at doses below 3-mu-g/kg, suggesting a saturable mechanism or different bioavailability. Only 0.001%-0.2% of the injected dose appeared in the urine as immunoreactive GM-CSF.