Pharmacokinetics of pegfilgrastim

Pegfilgrastim is a granulocyte colony-stimulating factor (G-CSF) with a long half-life and sustained duration of action. Pegfilgrastim is created with pegylation technology, whereby a 20-kD polyethylene glycol moiety is conjugated to filgrastim (recombinant human G-CSF), resulting in a larger molecule. Consequently, its renal clearance by glomerular filtration is minimized, making neutrophil-mediated clearance the predominant route of elimination. Preclinical animal data have shown that the clearance of pegfilgrastim depends on dosage and absolute neutrophil count, with pegfilgrastim having a longer circulating half-life and more sustained duration of action than filgrastim. The biologic effect of pegfilgrastim is prolonged in a neutropenic setting because few mature neutrophils are available to mediate its elimination. Clinical trials have suggested that neutrophil-mediated clearance of pegfilgrastim may be self-regulating and may therefore be specific to each patient's hematopoietic recovery.