| Primary information |
|---|
| ThPP ID | Th1082 |
| Therapeutic Peptide/Protein Name | Filgrastim |
| Sequence | MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVL view full sequnce in fasta |
| Functional Classification | 1b |
| Molecular Weight | 18800 |
| Chemical Formula | C845H1343N223O243S9 |
| Isoelectric Point | 5.65 |
| Hydrophobicity | 0.209 |
| Melting Point (℃) | 60 |
| Half Life | Elimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours; Elimination half- |
| Description | 175 amino acid long, recombinant human granulocyte colony stimulating factor (G-CSF) analogue expressed and purified from a strain of E. coli. Neupogen by Amgen. Amino acid sequence is identical to the natural sequence predicted in human genome, with the exception of an N-terminal methionine to aid 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. |
| Indication/Disease | 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. |
| Pharmacodynamics | Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Filgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. When tbo-filgrastim is administered to cancer patients, it took 3-5 days to reach maximum absolute neutrophil count (ANC). Levels of neutrophils returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16-19% increase in the ANCmax and a 33-36% increase in the area under the effect curve for ANC. |
| 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 |
| Toxicity | N.A. |
| Metabolism | N.A. |
| 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. |
| Volume of Distribution | Vd, healthy subjects and cancer patients = 150 mL/kg |
| Clearance | 0.5 - 0.7 mL/minute/kg (SC administration of 3.45 mcg/kg and 11.5 mcg/kg in both normal subjects and cancer patients, Neupogen) |
| Categories | Immunosuppressive Agents, Antineutropenic Agents and Hematopoietic Agents |
| Patents Number | CA1341537 |
| Date of Issue | 01/08/11 |
| Date of Expiry | 01/08/28 |
| Drug Interaction | Topotecan with Filgrastim may increase the adverse effects. Increased risk of prolonged neutropenia. Filgrastim should be administered at least 24 hours following Topotecan therapy. Monitor for signs and symptoms of neutropenia |
| Target | N.A. |
| Information of corresponding available drug in the market |
|---|
| Brand Name | N.A. |
| Company | N.A. |
| Brand Discription | N.A. |
| Prescribed for | N.A. |
| Chemical Name | N.A. |
| Formulation | N.A. |
| Physcial Appearnce | N.A. |
| Route of Administration | N.A. |
| Recommended Dosage | N.A. |
| Contraindication | N.A. |
| Side Effects | N.A. |
| Useful Link | N.A. |
| PubMed ID | 21456630, 25637379, 25631830, 25594147, 25581410, 25524005, 11677930 |
| 3-D Structure | Th1082 (View) or (Download) |