A phase I study to evaluate the clinical pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor

Aim To evaluate the pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in the prophylaxis of chemotherapy-induced neutropenia.Methods 24 patients received two cycles of the same chemotherapy regimen.In cycle 1,patients were just treated with chemotherapy.In cycle 2,patients would receive a single subcutaneous injection of PEG-rhG-CSF(dose levels of 60,100 or 150 μg·kg-1,8 patients in each group) 48 hours after chemotherapy.PEG-rhG-CSF was detected in the serum by ELISA.The pharmacokinetic parameters were calculated by WinNonlin 5.2.1,meanwhile pharmacodynamic analysis was performed.Results The main pharmacokinetic parameters of PEG-rhG-CSF after three single dose injection were as follows:T1 2 was(37.5±7),(40.8±12),(80.7±48) h;CL_F was(17±9),(9±4),(7±2) ml·h-1·g-1;AUC0-t was(5,593.6±5,435),(14,651.3±12,183),(23,002.5±6,655) mg·h·L-1.The mean ANC nadirs were 1.9×109 cells·L-1,2.3×109 cells·L-1,4.2×109 cells·L-1 in cycle 2,which were higher than those in cycle 1.Conclusions The pharmacokinetics of PEG-rhG-CSF is a non-linear profile.It has a potential of once-per-cycle administration.