Combination of a single SQ dose of SB-251353 after G-CSF treatment in Rhesus monkeys.
(A) Effects of the combination of 10 μg/kg G-CSF SQ for 4 days and a single SQ injection of 250 μg/kg SB-251353 on CFU mobilization in rhesus monkeys. Data represent the kinetics of mobilized CFU-GM (▪) and CFU-Meg (○) in response to G-CSF in combination with SB-251353, expressed as mean fold increase compared with G-CSF alone for 2 identically treated rhesus monkeys. Baseline and G-CSF–induced blood CFU-GM were on average 117 and 2194 CFU-GM/mL, respectively. There were no CFU-Meg colonies detected at baseline or after G-CSF treatment. Fold increases in CFU-Meg assumed a baseline of 1 CFU/mL. (B) Neutrophil counts following a single SQ injection of 250 μg/kg SB-251353 in G-CSF–pretreated rhesus monkeys. Two G-CSF–pretreated monkeys (10 μg/kg/d SQ for 4 days) were injected with a single dose of SB-251353 24 hours after the last G-CSF dose. Neutrophil counts were obtained at baseline (before G-CSF therapy began, 1.68 and 1.34 × 106 cells per mL, respectively) and immediately before SB-251353 injection (after G-CSF pretreatment, 16.51 and 7.52 × 106 cells per mL, respectively). Data are presented as the fold increase in neutrophil counts compared with G-CSF alone at the indicated times after SB-251353 administration.
