Chapter: Pharmaceutical Biotechnology: Fundamentals and Applications - Hematopoietic Growth Factors

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Pharmacodynamics

Filgrastim, Lenograstim, and Pegfilgrastim, Sargramostim and Molgramostim, Epoetin Alfa, Epoetin Beta, and Darbepoetin Alfa, Ancestim.

PHARMACODYNAMICS


Filgrastim, Lenograstim, and Pegfilgrastim

 

All three white cell factors increase neutrophil counts rapidly. Filgrastim and lenograstim have been shown to mobilize hematopoietic progenitor cells into the peripheral circulation. When filgrastim is discontin-ued, neutrophil counts return to baseline within approximately 4 days in most patients. A single dose of pegfilgrastim increases neutrophil count and CD34þ cell mobilization in a comparable or greater fashion than what is seen with filgrastim (Johnston et al., 2000).


Sargramostim and Molgramostim

 

Both sargramostim and molgramostim are multi-lineage HGFs and as such increase the number of granulocytes, monocytes, macrophages, and T-lymphocytes.


Epoetin Alfa, Epoetin Beta, and Darbepoetin Alfa

 

In patients with anemia due to chronic renal failure, administration of rhEPO (three times weekly) in-creases reticulocyte counts within 10 days. This reticulocyte increase is followed by increases in the red blood cell count, hemoglobin, and hematocrit within 2 to 6 weeks (Eschbach et al., 1989). Several studies with darbepoetin alfa in patients with renal failure or cancer show that red blood cell count is rapidly increased with the use of darbepoetin alfa (Macdougall et al., 1999; Glaspy et al., 2002; Vansteenkiste et al., 2002).


Ancestim

 

In phase I/II studies in patients with cancer, ancestim administered over a range of 5 to 25 mg/kg/day, in combination with fixed doses of filgrastim, produced a dose-dependent increase in circulating peripheral blood progenitor cells (PBPCs), including CD34þ cells, compared with the administration of ancestim alone (Glaspy et al., 1995). Patients receiving the cytokine combination had increases in circulating PBPCs that resulted in apheresis yields that were two- to threefold greater than those of patients receiving filgrastim alone.Oprelvekin

 

Oprelvekin administered daily for 14 days to patients who did not have myelosuppression from their chemotherapy caused platelet counts to increase in a dose-dependent manner (Orazi et al., 1995). Platelet counts began to increase between 5 and 9 days after the commencement of dosing; after the cessation of treatment, platelet counts continued to increase for another 7 days. No change in platelet aggregation or activation was noted. Healthy volunteers treated with oprelvekin had mean increases in plasma volume of >20%.

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