Peringatan Keamanan

The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.L40734

There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day.L40714

Filgrastim

DB00099

biotech approved

Deskripsi

Filgrastim is a short-acting recombinant, non-pegylated human granulocyte colony-stimulating factor (G-CSF) analog produced by recombinant DNA technology. It has an amino acid sequence identical to endogenous G-CSF, but it is non-glycosylated unlike the endogenous G-CSF and has an N-terminal methionine added in the sequence for expression in E. Coli.L40714 Human G-CSF is a glycoprotein that regulates the production and release of neutrophils from the bone marrow. Filgrastim mimics the biological actions of G-CSF to increase the levels of neutrophils in the blood.L40719 It has a number of therapeutic uses, including the management and prevention of infections and febrile neutropenia in patients receiving myelosuppressive chemotherapy or radiation therapy. It is also used to manage severe chronic neutropenia and mobilize hematopoietic progenitor cells to the peripheral blood for collection by leukapheresis in patients undergoing peripheral blood progenitor cell collection and therapy.L40714

Filgrastim was approved in the US in 1991 and there are biosimilars available with similar therapeutic indications.A245858 Tbo-filgrastim was approved by the FDA on August 29, 2012.L36325 Filgrastim-sndz was approved on March 6, 2015 L40768 and filgrastim-ayow was approved on March 2, 2022.L40773 A long-acting, pegylated G-CSF, pegfilgrastim, was made available to increase the duration of action of the drug.

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) After intravenous administration, the elimination half-life of filgrastim was approximately 3.5 hours in both normal subjects and patients with cancer. Single parenteral doses or daily intravenous doses‚ over a 14-day period‚ resulted in comparable half-lives. The half-lives were similar for intravenous administration (231 minutes‚ following doses of 34.5 mcg/kg) and for subcutaneous administration (210 minutes‚ following filgrastim dosages of 3.45 mcg/kg).[L40714]
Volume Distribusi After intravenous administration, the volume of distribution averaged 150 mL/kg.[L40714] There is no evidence of drug accumulation.[L40719]
Klirens (Clearance) Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration.[L40714]

Absorpsi

Filgrastim exhibits nonlinear pharmacokinetics. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70%.L40714

Metabolisme

Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive.A187841, A245878

Rute Eliminasi

There is limited information available; however, filgrastim is subject to renal elimination.A245878

Interaksi Obat

10 Data
Bleomycin The risk or severity of pulmonary toxicity can be increased when Filgrastim is combined with Bleomycin.
Cyclophosphamide The risk or severity of pulmonary toxicity can be increased when Filgrastim is combined with Cyclophosphamide.
Topotecan The risk or severity of neutropenia can be increased when Filgrastim is combined with Topotecan.
Vindesine The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vindesine.
Vinorelbine The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinorelbine.
Vincristine The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vincristine.
Vinblastine The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinblastine.
Vintafolide The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vintafolide.
Vinflunine The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinflunine.
Vincamine The risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vincamine.

Target Protein

Granulocyte colony-stimulating factor receptor CSF3R

Referensi & Sumber

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.
Artikel (PubMed)
  • PMID: 24237790
    Kamioner D, Fruehauf S, Maloisel F, Cals L, Lepretre S, Berthou C: Study design: two long-term observational studies of the biosimilar filgrastim Nivestim (Hospira filgrastim) in the treatment and prevention of chemotherapy-induced neutropenia. BMC Cancer. 2013 Nov 16;13:547. doi: 10.1186/1471-2407-13-547.
  • PMID: 18400509
    Panopoulos AD, Watowich SS: Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and 'emergency' hematopoiesis. Cytokine. 2008 Jun;42(3):277-88. doi: 10.1016/j.cyto.2008.03.002. Epub 2008 Apr 8.
  • PMID: 32644708
    Aghedo BO, Gupta V: Filgrastim .
  • PMID: 28939926
    Dale DC, Crawford J, Klippel Z, Reiner M, Osslund T, Fan E, Morrow PK, Allcott K, Lyman GH: A systematic literature review of the efficacy, effectiveness, and safety of filgrastim. Support Care Cancer. 2018 Jan;26(1):7-20. doi: 10.1007/s00520-017-3854-x. Epub 2017 Sep 22.
  • PMID: 11957188
    Boxer L, Dale DC: Neutropenia: causes and consequences. Semin Hematol. 2002 Apr;39(2):75-81. doi: 10.1053/shem.2002.31911.
  • PMID: 26105553
    Abdolzade-Bavil A, von Kerczek A, Cooksey BA, Kaufman T, Krasney PA, Pukac L, Gorlach M, Lammerich A, Scheckermann C, Allgaier H, Shen WD, Liu PM: Differential sensitivity of lipegfilgrastim and pegfilgrastim to neutrophil elastase correlates with differences in clinical pharmacokinetic profile. J Clin Pharmacol. 2016 Feb;56(2):186-94. doi: 10.1002/jcph.578. Epub 2015 Sep 1.
  • PMID: 19689472
    Scholz M, Ackermann M, Engel C, Emmrich F, Loeffler M, Kamprad M: A pharmacokinetic model of filgrastim and pegfilgrastim application in normal mice and those with cyclophosphamide-induced granulocytopaenia. Cell Prolif. 2009 Dec;42(6):813-22. doi: 10.1111/j.1365-2184.2009.00638.x. Epub 2009 Aug 17.

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