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 micrograms/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 greater than 1 ng/ml) was longer after a subcutaneous than after an intravenous injection. Area under the concentration-time curve (AUC), Cmax and t greater than 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 (t1/2) 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 micrograms/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.
Cebon
J S
JS
Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Australia.
Bury
R W
RW
Lieschke
G J
GJ
Morstyn
G
G
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy
D016178:Granulocyte-Macrophage Colony-Stimulating Factor