PHARMACOKINETIC STUDIES OF INTRAVENOUS GLYCOSYLATED RECOMBINANT HUMANGRANULOCYTE-COLONY-STIMULATING FACTOR IN VARIOUS HEMATOLOGICAL DISORDERS - INVERSE CORRELATION BETWEEN THE HALF-LIFE AND BONE-MARROW MYELOID CELL POOL

The pharmacokinetics of an intravenous bolus dose of glycosylated reco mbinant human G-CSF (rhG-CSF) was examined in 15 patients with various hematological disorders and 3 normal volunteers. The elimination half -life of rhG-CSF varied with the disorder. The half-life of an initial dose of rhG-CSF (2 mu g/weight kg) was significantly prolonged in pat ients with aplastic anemia (2.7 +/- 0.3 h, n = 3) and myelodysplastic syndrome-refractory anemia (2.0 +/- 0.3 h, n = 3) when compared with t hose in normal controls (0.9 +/- 0.5 h, n = 3). In contrast, in patien ts with acute myelogenous leukemia which was overt leukemia from myelo dysplastic syndrome-refractory anemia with excess of blasts in transfo rmation, the half-life was shortened after chemotherapy (0.2 +/- 0.1 h , n = 3). The half-life of rhG-CSF in 2 patients with acute lymphoblas tic leukemia in complete remission was prolonged (2.0 and 2.7 h) at th e time of marrow-suppression after chemotherapy and then shortened (0. 5, 1.0 h, respectively) in the recovery phase. The half-life of rhG-CS F was very weakly, inversely correlated with absolute neutrophil count in blood (n = 24, r(2) = 0.32, P < 0.01), and was inversely correlate d with the absolute count of bone-marrow myeloid cells (nucleated cell count in bone-marrow aspirates x the percentage of myeloid cells/100) of patients with aplastic anemia and myelodysplastic syndrome-refract ory anemia (n = 12, r(2) = 0.63, P = 0.002). These results suggest tha t the half-life of intravenously administered rhG-CSF (2 mu g/kg) refl ects the size of the myeloid cell compartment in vivo, and support the hypothesis that receptor-mediated consumption mainly accounts for the clearance of exogenous G-CSF. (C) 1997 Elsevier Science Ireland Ltd.