G-CSF SERUM PHARMACOKINETICS DURING PERIPHERAL-BLOOD PROGENITOR-CELL MOBILIZATION - NEUTROPHIL COUNT-ADJUSTED DOSAGE MIGHT POTENTIALLY IMPROVE MOBILIZATION AND BE MORE COST-EFFECTIVE

The optimal dosing schedule of G-CSF for peripheral blood progenitor c ell (PBPC) mobilization is still under investigation although many cen ters use 10 mu g/kg/day in a single subcutaneous dose. However, G-CSF clearance increases with increasing absolute neutrophil count (ANC). H ence a G-CSF dosage adjusted to ANC might be a reasonable approach. We measured G-CSF trough serum levels by sandwich ELISA assay at differe nt ANCs in eight patients undergoing treatment with filgrastim at 10 m u g/kg/day in a single subcutaneous dose. A total of 26 samples were a nalyzed, and a strong correlation between increasing ANC and decreasin g G-CSF levels was found by linear regression analysis (P < 0.0003, r( 2) = 0.4199). For ANC values above 5000/mu l the trough serum levels, ie 24 h after administration, were consistently below the level that p rovides maximal clonogenic precursor stimulation in vitro (10 ng/ml). Serial serum G-CSF measurements performed in three patients at 0, 3, 6 , 9 and 24 h after G-CSF administration, showed a reduction of the are a under the curve (AUC) with increasing ANC. For an ANC of 20 000/mu l or greater, the G-CSF serum level fell under the maximal in vitro sti mulation threshold of 10 ng/ml within 12 h. This preliminary pharmacok inetic data seems to suggest that an ANC-adjusted G-CSF dosing schedul e might improve the design of PBPC mobilization regimens.