Lutholaz Mechanism of Action

Pharmacotherapeutic group: Immunostimulants, colony stimulating factor. ATC Code: L03AA13.
Pharmacology: Pharmacodynamics: Human granulocyte colony stimulating factor (G-CSF) is a glycoprotein, which regulates the production and release of neutrophils from the bone marrow. Pegfilgrastim is a covalent conjugate of recombinant human G-CSF (r-metHuG-CSF) with a single 20 kd polyethylene glycol (PEG) molecule. Pegfilgrastim is a sustained duration form of filgrastim due to decreased renal clearance.
Pegfilgrastim and filgrastim have been shown to have identical modes of action, causing a marked increase in peripheral blood neutrophil counts within 24 hours, with minor increases in monocytes and/or lymphocytes. Similarity to filgrastim, neutrophils produced in response to pegfilgrastim show normal or enhanced function as demonstrated by tests of chemotactic and phagocytic function. As with other haematopoietic growth factors, G-CSF has shown in vitro stimulating properties on human endothelial cells. G-CSF can promote growth of myeloid cells, including malignant cells, in vitro and similar effects may be seen on some non-myeloid cells in vitro.
Pharmacokinetics: Absorption: After a single subcutaneous dose of pegfilgrastim, the peak serum concentration of pegfilgrastim occurs at 16 to 120 hours after dosing.
Distribution: Serum concentrations of pegfilgrastim are maintained during the period of neutropenia after myelosuppressive chemotherapy.
Elimination: The elimination of pegfilgrastim is non-linear with respects to dose; serum clearance of pegfilgrastim decreases with increasing dose. Pegfilgrastim appears to be mainly eliminated by neutrophil mediated clearance (>99%), which becomes saturated at higher doses. Consistent with a self-regulating clearance mechanism, the serum concentration of pegfilgrastim declines rapidly at the onset of neutrophil recovery.
Pharmacokinetics in special populations: Due to the neutrophil-mediated clearance mechanism, the pharmacokinetics of pegfilgrastim is not expected to be affected by renal or hepatic impairment.
Limited data indicate that the pharmacokinetics of pegfilgrastim in elderly subjects (>65 years) is similar to that in adults.
The pharmacokinetics of pegfilgrastim were studied in 37 paediatric patients with sarcoma, who received 100 μg/kg pegfilgrastim after the completion of VAdriaC/IE chemotherapy. The youngest age group (0-5 years) had a higher mean exposure to pegfilgrastim (AUC) (± Standard Deviation) (47.9 ± 22.5 μg·hr/ml) than older children aged 6-11 years and 12-21 years (22.0 ± 13.1 μg·hr/ml and 29.3 ± 23.2 μg·hr/ml, respectively). With the exception of the youngest age group (0-5 years), the mean AUC in paediatric subjects appeared similar to that for adult patients with high-risk stage II-IV breast cancer and receiving 100 μg/kg pegfilgrastim after the completion of doxorubicin/docetaxel.