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Identification
NameFilgrastim
Accession NumberDB00099  (BTD00072, BIOD00072)
TypeBiotech
GroupsApproved
DescriptionFilgrastim 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. On March 6, 2015, the FDA approved the biosimilar Zarxio (filgrastim-sndz) and is indicated for use in the same conditions as Neupogen. Zarxio is marketed by Sandoz.
Protein structureDb00099
Related Articles
Protein chemical formulaC845H1343N223O243S9
Protein average weight18800.0 Da
Sequences
>Amino acid sequence for filgrastim
MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWA
PLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQ
QMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Download FASTA Format
Synonyms
G-CSF
Granulocyte Colony Stimulating Factor
Tbo-filgrastim
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Granixinjection, solution480 ug/.8mLsubcutaneousCephalon, Inc.2013-11-11Not applicableUs
Granixinjection, solution300 ug/.5mLsubcutaneousCephalon, Inc.2013-11-11Not applicableUs
Grastofilsolution300 mcgintravenous; subcutaneousApotex Inc2016-03-17Not applicableCanada
Neupogensolution600 mcgintravenous; subcutaneousAmgen Canada Inc2016-02-02Not applicableCanada
Neupogeninjection, solution300 ug/mLintravenousPhysicians Total Care, Inc.1994-06-08Not applicableUs
Neupogeninjection, solution480 ug/.8mLintravenousPhysicians Total Care, Inc.2006-08-14Not applicableUs
Neupogensolution300 mcgintravenous; subcutaneousAmgen Canada Inc1992-12-31Not applicableCanada
Neupogeninjection, solution300 ug/.5mLintravenousPhysicians Total Care, Inc.2004-03-11Not applicableUs
Neupogensolution600 mcgintravenous; subcutaneousAmgen Canada Inc2016-01-28Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BiocilinNot Available
BiofigranNot Available
BiofilgranNot Available
EndufilNot Available
FilatilNot Available
FilgenNot Available
GranNot Available
GranulokineNot Available
GrimatinNot Available
InmunefNot Available
JiexinNot Available
LeucogenNot Available
LeucostimNot Available
MacroleucoNot Available
NeukineNot Available
NeutromaxNot Available
Neutroval Sicor Biotech
NivestimNot Available
RecombicyteNot Available
SciLocyteNot Available
TevagastrimNot Available
White-C Not Available
ZarzioNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIPVI5M0M1GW
CAS number121181-53-1
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFilgrastim 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.
PharmacodynamicsUsed 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 actionFilgrastim 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
Related Articles
AbsorptionAbsorption 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

Protein bindingNot Available
MetabolismNot Available
Route of eliminationFilgrastim 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.
Half lifeElimination half-life, healthy subjects and cancer patients, Neopogen = 3.5 hours; Elimination half-life, cancer patients, tbo-filgrastim = 3.2-3.8 hours
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)

ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, solutionsubcutaneous300 ug/.5mL
Injection, solutionsubcutaneous480 ug/.8mL
Injection, solutionintravenous300 ug/mL
Injection, solutionintravenous300 ug/.5mL
Injection, solutionintravenous480 ug/.8mL
Solutionintravenous; subcutaneous300 mcg
Solutionintravenous; subcutaneous600 mcg
Prices
Unit descriptionCostUnit
Neupogen 480 mcg/0.8ml Solution 1 Box Contains Ten 0.8ml Syringes4998.24USD box
Neupogen 480 mcg/1.6ml Solution 1 Box Contains Ten 1.6ml Syringes4554.58USD box
Neupogen 300 mcg/0.5ml Solution 1 Box Contains Ten 0.5ml Syringes3138.1USD box
Neupogen 480 mcg/1.6 ml vial437.94USD ml
Neupogen 300 mcg/ml vial286.04USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1339071 No1997-07-292014-07-29Canada
CA1341537 No2007-07-312024-07-31Canada
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point60 °CLuo, P., Protein Science 11:1218-1226 (2002)
hydrophobicity0.209Not Available
isoelectric point5.65Not Available
References
Synthesis Reference

Tetsuro Kuga, Hiromasa Miyaji, Moriyuki Sato, Masami Okabe, Makoto Morimoto, Seiga Itoh, Motoo Yamasaki, Yoshiharu Yokoo, Kazuo Yamaguchi, Hajime Yoshida, Yoshinori Komatsu, “Method of producing a polypeptide having human granulocyte colony stimulating factor activity.” U.S. Patent US5994518, issued February, 1988.

US5994518
General References
  1. Wang B, Ludden TM, Cheung EN, Schwab GG, Roskos LK: Population pharmacokinetic-pharmacodynamic modeling of filgrastim (r-metHuG-CSF) in healthy volunteers. J Pharmacokinet Pharmacodyn. 2001 Aug;28(4):321-42. [PubMed:11677930 ]
External Links
ATC CodesL03AA02
AHFS Codes
  • 20:16.00
PDB Entries
FDA labelDownload (769 KB)
MSDSDownload (125 KB)
Interactions
Drug Interactions
Drug
BleomycinThe risk or severity of adverse effects can be increased when Filgrastim is combined with Bleomycin.
CyclophosphamideThe risk or severity of adverse effects can be increased when Filgrastim is combined with Cyclophosphamide.
TopotecanThe risk or severity of adverse effects can be increased when Filgrastim is combined with Topotecan.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
stimulator
General Function:
Receptor activity
Specific Function:
Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differientation and survival of cells along the neutrophilic lineage. In addition it may function in some adhesion or recognition events at the cell surface.
Gene Name:
CSF3R
Uniprot ID:
Q99062
Molecular Weight:
92155.615 Da
References
  1. Erkeland SJ, Aarts LH, Irandoust M, Roovers O, Klomp A, Valkhof M, Gits J, Eyckerman S, Tavernier J, Touw IP: Novel role of WD40 and SOCS box protein-2 in steady-state distribution of granulocyte colony-stimulating factor receptor and G-CSF-controlled proliferation and differentiation signaling. Oncogene. 2007 Mar 29;26(14):1985-94. Epub 2006 Sep 25. [PubMed:17001306 ]
  2. Link DC, Kunter G, Kasai Y, Zhao Y, Miner T, McLellan MD, Ries RE, Kapur D, Nagarajan R, Dale DC, Bolyard AA, Boxer LA, Welte K, Zeidler C, Donadieu J, Bellanne-Chantelot C, Vardiman JW, Caligiuri MA, Bloomfield CD, DiPersio JF, Tomasson MH, Graubert TA, Westervelt P, Watson M, Shannon W, Baty J, Mardis ER, Wilson RK, Ley TJ: Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia. Blood. 2007 Sep 1;110(5):1648-55. Epub 2007 May 9. [PubMed:17494858 ]
  3. Cao YR, Shao ZH, Liu H, Shi J, Bai J, Tu MF, Wang HQ, Xing LM, Cui ZZ, Sun J, Jia HR, Yang TY: [The response of bone marrow hematopoietic cells to G-CSF in paroxysmal nocturnal hemoglobinuria patients]. Zhonghua Xue Ye Xue Za Zhi. 2005 Apr;26(4):235-8. [PubMed:15949269 ]
  4. Ward AC: The role of the granulocyte colony-stimulating factor receptor (G-CSF-R) in disease. Front Biosci. 2007 Jan 1;12:608-18. [PubMed:17127322 ]
  5. Zhuang D, Qiu Y, Haque SJ, Dong F: Tyrosine 729 of the G-CSF receptor controls the duration of receptor signaling: involvement of SOCS3 and SOCS1. J Leukoc Biol. 2005 Oct;78(4):1008-15. Epub 2005 Jul 20. [PubMed:16033816 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other/unknown
General Function:
Serine-type endopeptidase activity
Specific Function:
Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.
Gene Name:
ELANE
Uniprot ID:
P08246
Molecular Weight:
28517.81 Da
References
  1. Carter CR, Whitmore KM, Thorpe R: The significance of carbohydrates on G-CSF: differential sensitivity of G-CSFs to human neutrophil elastase degradation. J Leukoc Biol. 2004 Mar;75(3):515-22. Epub 2003 Dec 4. [PubMed:14657210 ]
  2. Jian MY, Koizumi T, Tsushima K, Fujimoto K, Kubo K: Effects of granulocyte colony-stimulating factor (G-CSF) and neutrophil elastase inhibitor (ONO-5046) on acid-induced lung injury in rats. Inflammation. 2004 Dec;28(6):327-36. [PubMed:16245075 ]
  3. Donini M, Fontana S, Savoldi G, Vermi W, Tassone L, Gentili F, Zenaro E, Ferrari D, Notarangelo LD, Porta F, Facchetti F, Notarangelo LD, Dusi S, Badolato R: G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms. Blood. 2007 Jun 1;109(11):4716-23. Epub 2007 Feb 20. [PubMed:17311988 ]
  4. Schepers H, Wierenga AT, van Gosliga D, Eggen BJ, Vellenga E, Schuringa JJ: Reintroduction of C/EBPalpha in leukemic CD34+ stem/progenitor cells impairs self-renewal and partially restores myelopoiesis. Blood. 2007 Aug 15;110(4):1317-25. Epub 2007 May 2. [PubMed:17475913 ]
  5. Druhan LJ, Ai J, Massullo P, Kindwall-Keller T, Ranalli MA, Avalos BR: Novel mechanism of G-CSF refractoriness in patients with severe congenital neutropenia. Blood. 2005 Jan 15;105(2):584-91. Epub 2004 Sep 7. [PubMed:15353486 ]
  6. El Ouriaghli F, Fujiwara H, Melenhorst JJ, Sconocchia G, Hensel N, Barrett AJ: Neutrophil elastase enzymatically antagonizes the in vitro action of G-CSF: implications for the regulation of granulopoiesis. Blood. 2003 Mar 1;101(5):1752-8. Epub 2002 Oct 17. [PubMed:12393522 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23