Pharmacokinetics of human granulocyte-macrophage colony-stimulating factor using a sensitive immunoassay.
A sensitive and reliable sandwich enzyme-linked immunosorbent assay (ELISA) has been developed for recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The assay is quantitative between 100 pg/mL and 2.5 ng/mL for bacterially synthesized hGM-CSF in human serum and is more sensitive and specific than the semisolid agar bioassay. As part of a phase I study, the pharmacokinetics of intravenous (IV) bolus injection and subcutaneous (SC) administration of hGM-CSF were studied. Following a single IV dose, an initial high blood level of hGM-CSF occurred, followed by a rapid decrease occurring in two apparent phases with a half-life (t1/2)alpha of less than five minutes and a t1/2 beta of 150 minutes. After an SC injection, detectable serum levels occurred within 15 to 30 minutes, and serum levels were sustained for a variable time depending on the dose. At the highest SC dose (10 micrograms/kg), a serum level of greater than 1 ng/mL (65 pmol/L) was maintained for greater than 12 hours after a single injection. This corresponds to the concentration of hGM-CSF supporting near-maximum proliferation in vitro.
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal; D001853:Bone Marrow / Q000473:pathology; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000493:pharmacokinetics*; D004341:Drug Evaluation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000493:pharmacokinetics*; D006801:Humans; D007106:Immune Sera; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011817:Rabbits; D011994:Recombinant Proteins / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007106:Immune Sera; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor