Pharmacokinetics of Human Granulocyte-Macrophage Colony-Stimulating Factor Using A Sensitive Immunoassay

• Published in: Blood Vol. 72; no. 4; pp. 1340 - 1347
• Main Authors: Cebon, Jonathan, Dempsey, Peter, Fox, Richard, Kannourakis, George, Bonnem, Eric, Burgess, Antony W., Morstyn, George
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-10-1988; The Americain Society of Hematology
• Subjects: Adult; Aged; Animals; Antibodies, Monoclonal; Biological and medical sciences; Bone Marrow - pathology; Colony-Forming Units Assay; Colony-Stimulating Factors - pharmacokinetics; Drug Evaluation; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances - pharmacokinetics; Humans; Immune Sera; Injections, Intravenous; Male; Mice; Mice, Inbred BALB C; Middle Aged; Rabbits; Recombinant Proteins - pharmacokinetics; Vertebrates: blood, hematopoietic organs, reticuloendothelial system
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V72.4.1340.1340

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 β repid decrease occurring in two apparent phases with a half-life (t½)α of less than five minutes and a t½β 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 µg/kg), a serum level of >1 ng/mL (65 pmol/L) was maintained for >12 hours after a single injection. This corresponds to the concentration of hGM-CSF supporting near-maximum proliferation in vitro.