PHARMACOKINETICS OF HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR USING A SENSITIVE IMMUNOASSAY

  • 1 October 1988
    • journal article
    • research article
    • Vol. 72  (4) , 1340-1347
Abstract
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 .mu.g/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.