Pharmacokinetics And Pharmacodynamics Of Two Formulations Of Pegylated Recombinant Human Granulocyte Colony-Stimulating Factor In Healthy Chinese Subjects: An Open-Label, Randomized, Parallel-Design Bioavailability Study

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, pegfilgrastim) is a long-acting derivative of recombinant human granulocyte colony-stimulating factor with limited renal clearance and a longer half-life. It is used for the prevention of febrile neutropenia, owing to its capacity to promote neutrophil recovery. In this study, the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of 2 formulations of PEG-rhG-CSF were evaluated in healthy Chinese subjects. Twenty-four male subjects who received a single dose of subcutaneous PEG-rhG-CSF 100 mu g/kg were randomized to either treatment A (3 mg/mL) or treatment B (1 mg/mL). Noncompartmental pharmacokinetic parameters of PEG-rhG-CSF were derived from serum concentration-time data. In addition, absolute neutrophil count (ANC) as a pharmacodynamic maker, immunogenicity through antidrug antibody testing, and safety were evaluated. The mean area under the concentration-time curve from time zero to the last quantifiable concentration (AUC(0-t)) and the mean maximum concentration (C-max) of PEG-rhG-CSF after treatment A were 5070 ng center dot h/mL and 125 ng/mL, respectively; these values were comparable to those measured after treatment B (5340 ng center dot h/mL and 123 ng/mL, respectively). The mean value of area under the oANC (baseline-adjusted ANC)-time curve and the maximum oANC values were 4380 x 10(9) h/L and 33.1 x 10(9)/L, respectively, in the treatment A group, and 5170 x 10(9) h/L and 38.6 x 10(9)/L, respectively, in the treatment B group. The pharmacokinetic and pharmacodynamic profiles were similar for the 2 PEG-rhG-CSF formulations following a single dose of 100 mu g/kg. The safety and immunogenicity profiles were also similar, with no significant differences. The dose adjustment of PEG-rhG-CSF was not considered necessary for formulation transformation.