1. Pegfilgrastim Drugbank ID : DB00019
Protein chemical formula : C845H1343N223O243S9
Protein average weight :
Half life : hrs

2. Description : Indication : Pharmacodynamics :
PEGylated (at N terminus) form of human G-CSF (Granulocyte colony stimulating factor), 175 residues, produced from E. coli via bacterial fermentation.
Indication :
Increases leukocyte production, for treatment in non-myeloid cancer, neutropenia and bone marrow transplant
Pharmacodynamics :
Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Pegfilgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. Pegfilgrastim has reduced renal clearance and prolonged persistence in vivo as compared to Filgrastim..

3. Mechanism of action :
Pegfilgrastim binds to the G-CSF receptor. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Pegfilgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Pegfilgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, pegfilgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase

4. Route of Elimination : Targets :
Filgrastim is primarily eliminated by the kidney and neutrophils/neutrophil precursors; the latter presumably involves binding of the growth factor to the G-CSF receptor on the cell surface, internalization of the growth factor-receptor complexes via endocytosis, and subsequent degradation inside the cells. Pegylation of filgrastim renders renal clearance insignificant, which was demonstrated in bilaterally nephrectomized rats and confirmed in subjects with renal impairment. As a result, the neutrophil-mediated clearance is the predominant elimination pathway for pegfilgrastim. During chemotherapy-induced neutropenia, the clearance of pegfilgrastim is significantly reduced and the concentration of pegfilgrastim is sustained until onset of neutrophil recovery.
Targets :
Granulocyte colony-stimulating factor receptor,Neutrophil elastase

5. Categories :
Immunosuppressive Agents and Antineutropenic Agents
Patents :
Country Patent Number Approved Expires
Canada
Canada

6. Brands : Neulasta
Company : Amgen Inc.
Description : Neulasta (pegfilgrastim) is a covalent conjugate of recombinant methionyl human G-CSF (filgrastim) and monomethoxypolyethylene glycol. Filgrastim is a water-soluble 175 amino acid protein with a molecular weight of approximately 19 kilodaltons (kD). Filgrastim is obtained from the bacterial fermentation of a strain of E coli transformed with a genetically engineered plasmid containing the human G-CSF gene. To produce pegfilgrastim, a 20 kD monomethoxypolyethylene glycol molecule is covalently bound to the N-terminal methionyl residue of filgrastim. The average molecular weight of pegfilgrastim is approximately 39 kD
Used for/Prescribed for : Neulasta is used to prevent neutropenia, a lack of certain white blood cells caused by receiving chemotherapy.
Formulation : supplied in 0.6 mL prefilled syringes. ach syringe contains 6 mg pegfilgrastim (based on protein weight) in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), polysorbate 20 (0.02 mg), sodium (0.02 mg), and sorbitol (30 mg) in Water for Injection, USP
Form : solution
Route of administration : subcutaneous injection

7. Dosage : The recommended dosage of Neulasta is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle in adults. Do not administer Neulasta between 14 days before and 24 hours after administration of cytotoxic chemotherapy. Contraindication : allergy, or having sickle cell disorder; chronic myeloid leukemia Side effects : Common Neulasta side effects may include: bone pain Drug interaction : A total of 107 drugs (254 brand and generic names) showing moderate interctions are known to interact with Neulasta (pegfilgrastim)

8. General references :
# Yang BB, Kido A: Pharmacokinetics and pharmacodynamics of pegfilgrastim. Clin Pharmacokinet May 1;50(5): doi: / "Pubmed":

9. References : http://www. drugs. com/neulasta. html http://www. drugs