TY - JOUR
T1 - The effects of dose and route of the administration on the pharmacokinetics of granulocyte-macrophage colony-stimulating factor
AU - Cebon, Jonathan Simon
AU - Bury, Ross William
AU - Lieschke, Graham John
AU - Morstyn, George
PY - 1990
Y1 - 1990
N2 - The pharmacokinetics of granulocyte-macrophage colony stimulating factor (GM-CSF) (0.3-30 μg/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 (Cmax) 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), Cmax 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 μg/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.
AB - The pharmacokinetics of granulocyte-macrophage colony stimulating factor (GM-CSF) (0.3-30 μg/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 (Cmax) 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), Cmax 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 μg/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.
UR - http://www.scopus.com/inward/record.url?scp=0025674341&partnerID=8YFLogxK
U2 - 10.1016/0277-5379(90)90053-V
DO - 10.1016/0277-5379(90)90053-V
M3 - Article
C2 - 2148882
AN - SCOPUS:0025674341
VL - 26
SP - 1064
EP - 1069
JO - European Journal of Cancer and Clinical Oncology
JF - European Journal of Cancer and Clinical Oncology
SN - 0277-5379
IS - 10
ER -