Lenograstim Other names: rHuG-CSF

Lenograstim (rHuG-CSF) belongs to the cytokine group of biologically active proteins which regulate cell differentiation and cell growth.

rHuG-CSF is a factor that stimulates neutrophil precursor cells as demonstrated by the CFU-S and CFU-GM cell count which increases in peripheral blood. Lenograstim induces a marked increase in peripheral blood neutrophil counts within 24 hours of administration.

Pharmacodynamic effects

Elevations of neutrophil count are dose-dependent over the 1-10 µg/kg/day range. At the recommended dose, repeated doses induce an enhancement of the neutrophil response. Neutrophils produced in response to lenograstim show normal chemotactic and phagocytic functions. As with other hematopoietic growth factors, G-CSF has shown in vitro stimulating properties on human endothelial cells.

Absorption and Distribution

The pharmacokinetics of lenograstim are dose and time dependent.

During repeated dosing (IV and SC routes), peak serum concentration (immediately after IV infusion or after SC injection) is proportional to the injected dose. Repeated dosing with lenograstim by the two administration routes showed no evidence of drug accumulation.

At the recommended dose, the absolute bioavailability of lenograstim is 30%. The apparent volume of distribution (Vd) is approximately 1 L/kg body weight and the mean residence time close to 7 h following subcutaneous dosing.

Elimination

The apparent serum elimination half-life of lenograstim (S.C. route) is about 3-4 h, at steady state (repeated dosing) and is shorter (1-1.5 h) following repeated IV infusion.

Plasma clearance of rHuG-CSF increased 3-fold (from 50 up to 150 mL/min) during repeated S.C. dosing. Less than 1% of lenograstim is excreted in urine unchanged and it is considered to be metabolised to peptides. During multiple S.C. dosing, peak serum concentrations of lenograstim are close to 100 pg/mL/kg body weight at the recommended dosage. There is a positive correlation between the dose and the serum concentration of lenograstim and between the neutrophil response and the total amount of lenograstim recovered in serum.

In animals, acute toxicity studies (up to 1000 µg/kg/day in mice) and sub-acute toxicity studies (up to 100 µg/kg/day in monkey) showed the effects of overdose were restricted to an exaggerated and reversible pharmacological effect.

There is no evidence from studies in rats and rabbits that lenograstim is teratogenic. An increased incidence of embryo-loss has been observed in rabbits, but no malformation has been seen.