DB00099 - Filgrastim
| Identification | |||||
|---|---|---|---|---|---|
| Name | Filgrastim | ||||
| Accession Number | DB00099 (BIOD00072, BTD00072) | ||||
| Type | biotech | ||||
| Description | Filgrastim is a recombinant, non-pegylated human granulocyte colony stimulating factor (G-CSF) analogue manufactured by recombinant DNA technology using a strain of E. coli. It is marketed as the brand name Neupogen by Amgen. Chemically, it consists of 175 amino acid residues. The protein has an amino acid sequence that is identical to the natural sequence predicted from human DNA sequence analysis, except for the addition of an N-terminal methionine necessary for expression in E coli. Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting. | ||||
| Structure |
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| Categories (*) | |||||
| Molecular Weight | 18.8 kDa | ||||
| Groups | approved | ||||
| Monoisotopic Weight | Not Available | ||||
| Pharmacology | |||||
| Indication | Filgrastim is used in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. It is also used in cancer patients receiving bone marrow transplant. In general, filgrastim increases neutrophil counts in order to decrease the risk of infection or duration of neutropenia in the aforementioned patient populations. Infection and neutropenia are adverse events associated with chemotherapy. Furthermore, filgrastim is also indicated for patients with severe chronic neutropenia. It mobilizes hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis to allow for a more rapid engraftment. Tbo-filgrastim has a narrower indication profile than Neupogen - it is a leukocyte growth factor indicated for the reduction in the duration of severe neutropenia in patients with non-myeloid malignancies. | ||||
| Mechanism of action | Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Filgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, Filgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase | ||||
| Absorption | Absorption and clearance of Neupogen follows first-order pharmacokinetic modeling without apparent concentration dependence. When 3.45 mcg/kg and 11.5 mcg/kg of Neupogen is subcutaneously administered, the maximum serum concentration is 4 and 49 ng/mL, respectively, within 2 to 8 hours. Neupogen does not accumulate. It is estimated that when filgrastim is subcutaneously administered, the absolute bioavailability is approximately 62% and 71% for 375 mcg and 750 mcg doses respectively. When 5 mcg/kg tbo-filgrastim is subcutaneously administered, the absolute bioavailability is 33%. It takes 4-6 hours for tho-filgrastim to reach maximum concentration. Like Neupogen, accumulation was not observed. | ||||
| Protein binding | Not Available | ||||
| Biotransformation | Not Available | ||||
| Route of elimination | 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. | ||||
| Toxicity | Not Available | ||||
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| Interactions | |||||
| Drug Interactions |
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| Food Interactions | Not Available | ||||
Targets
| Granulocyte colony-stimulating factor receptor | |
|---|---|
| Name | Granulocyte colony-stimulating factor receptor |
| Gene Name | CSF3R |
| Pharmacological action | yes |
| Actions | stimulator |
| References |
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| DTHybrid score | 1.409 |
| Leukocyte elastase | |
| Name | Leukocyte elastase |
| Gene Name | ELANE |
| Pharmacological action | unknown |
| Actions | other/unknown |
| References |
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| DTHybrid score | 1.9087 |
Predictions
| Id | Partner name | Gene Name | Score |
|---|---|---|---|
| 6260 | Chymotrypsin-like elastase family member 1 | CELA1 | 0.2672 |