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词条 Peginterferon alfa-2b
释义

  1. Medical uses

      Host genetic factors 

  2. Side effects

  3. Mechanism of action

  4. History

  5. References

  6. External links

{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 470447710
| IUPAC_name = PEGylated human interferon alpha 2b
| image =
| tradename = PegIntron, Sylatron, ViraferonPeg, others
| Drugs.com = {{drugs.com|ppa|peginterferon-alfa-2b}}
| MedlinePlus = a605030
| pregnancy_AU =
| pregnancy_US =
| pregnancy_category = C, X (with ribavirin)
| licence_EU = yes
| legal_AU =
| legal_UK =
| legal_US =
| legal_status =
| routes_of_administration = subQ
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life = 22–60 hrs
| excretion =
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 99210-65-8
| ATC_prefix = L03
| ATC_suffix = AB10
| PubChem =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00022
| IUPHAR_ligand = 7462
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = G8RGG88B68
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02745
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1201561
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| C=860 | H=1353 | N=229 | O=255 | S=9
| molecular_weight = 19269.1 g/mol
}}Pegylated interferon alfa-2b, sold under the brand name PegIntron among others, is a medication used to treat hepatitis C and melanoma.[1] For hepatitis C it is typically used with ribavirin and cure rates are between 33 and 82%.[1][1] For melanoma it is used in addition to surgery.[1] It is given by injection under the skin.[2]

Side effects are common.[6] They may include headache, feeling tired, mood changes, trouble sleeping, hair loss, nausea, pain at the site of injection, and fever.[2] Severe side effects may include psychosis, liver problems, blood clots, infections, or an irregular heartbeat.[2] Use with ribavirin is not recommended during pregnancy.[2] Pegylated interferon alfa-2b is in the alpha interferon family of medications.[2] It is pegylated to protects the molecule from breakdown.[6]

Pegylated interferon alfa-2b was approved for medical use in the United States in 2001.[2] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] The wholesale cost in the developing world is between 500 and 4,800 USD for 12 weeks.[4] In the United States this costs about 8,400.00 USD,[5] while in the United Kingdom 12 weeks costs the NHS about 1595.00 pounds.[6]

Medical uses

It is used to treat hepatitis C and melanoma. For hepatitis C it is typically used with ribavirin. For melanoma it is used in addition to surgery.[2]

For hepatitis C it may also be used with boceprevir, telaprevir, simeprevir, or sofosbuvir.[5]

Host genetic factors

For genotype 1 hepatitis C treated with pegylated interferon-alfa-2a or pegylated interferon-alfa-2b combined with ribavirin, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon lambda 3, are associated with significant differences in response to the treatment. This finding, originally reported in Nature,[7] showed that genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene are more likely to achieve sustained virological response after the treatment than others. A later report from Nature[8] demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus.

Side effects

Common side effects include headache, feeling tired, mood changes, trouble sleeping, hair loss, nausea, pain at the site of injection, and fever. Severe side effects may include psychosis, liver problems, blood clots, infections, or an irregular heartbeat.[2] Use with ribavirin is not recommended during pregnancy.[2]

Mechanism of action

One of the major mechanisms of PEG-interferon alpha-2b utilizes the JAK-STAT signaling pathway. The basic mechanism works such that PEG-interferon alpha-2b will bind to its receptor, interferon-alpha receptor 1 and 2 (IFNAR1/2). Upon ligand binding the Tyk2 protein associated with IFNAR1 is phosphorylated which in turn phosphorylates Jak1 associated with IFNAR2. This kinase continues its signal transduction by phosphorylation of signal transducer and activator of transcription (STAT) 1 and 2 via Jak 1 and Tyk2 respectively. The phosphorylated STATs then dissociate from the receptor heterodimer and form an interferon transcription factor with p48 and IRF9 to form the interferon stimulate transcription factor-3 (ISGF3). This transcription factor then translocates to the nucleus where it will transcribe several genes involved in cell cycle control, cell differentiation, apoptosis, and immune response.[9][10]

PEG-interferon alpha-2b acts as a multifunctional immunoregulatory cytokine by transcribing several genes, including interleukin 4 (IL4). This cytokine is responsible for inducing T helper cells to become type 2 helper T cells. This ultimately results in the stimulation of B cells to proliferate and increase their antibody production. This ultimately allows for an immune response, as the B cells will help to signal the immune system that a foreign antigen is present.[11]

Another major mechanism of type I interferon alpha (IFNα) is to stimulate apoptosis in malignant cell lines. Previous studies have shown that IFNα can cause cell cycle arrest in U266, Daudi, and Rhek-1 cell lines.[12]

A follow-up study researched to determine if the caspases were involved in the apoptosis seen in the previous study as well as to determine the role of mitochondrial cytochrome c release. The study confirmed that there was cleavage of caspase-3, -8, and -9. All three of these cysteine proteases play an important role in the initiation and activation of the apoptotic cascade. Furthermore, it was shown that IFNα induced a loss in the mitochondrial membrane potential which resulted in the release of cytochrome c from the mitochondria. Follow-up research is currently being conducted to determine the upstream activators of the apoptotic pathway that are induced by IFNα.[13]

History

It was developed by Schering-Plough. Merck studied it for melanoma under the brand name Sylatron. It was approved for this use in April 2011.

References

1. ^{{cite web|title=ViraferonPeg Pen 50, 80, 100, 120 or 150 micrograms powder and solvent for solution for injection in pre-filled pen CLEAR CLICK - Summary of Product Characteristics (SPC) - (eMC)|url=https://www.medicines.org.uk/emc/medicine/28182|website=www.medicines.org.uk|accessdate=12 January 2017|deadurl=no|archiveurl=https://web.archive.org/web/20170113132453/https://www.medicines.org.uk/emc/medicine/28182|archivedate=13 January 2017|df=}}
2. ^1 2 3 4 5 6 7 8 9 10 11 12 13 14 {{cite web|title=Peginterferon Alfa-2b (Professional Patient Advice) - Drugs.com|url=https://www.drugs.com/ppa/peginterferon-alfa-2b.html|website=www.drugs.com|accessdate=12 January 2017|deadurl=no|archiveurl=https://web.archive.org/web/20170116190131/https://www.drugs.com/ppa/peginterferon-alfa-2b.html|archivedate=16 January 2017|df=}}
3. ^{{cite web|title=WHO Model List of Essential Medicines (19th List)|url=http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|work=World Health Organization|accessdate=8 December 2016|date=April 2015|deadurl=no|archiveurl=https://web.archive.org/web/20161213052708/http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|archivedate=13 December 2016|df=}}
4. ^{{cite web|title=Inclusion of the injectable formulation of peginterferon alfa-2a and -2b is proposed for the treatment of hepatitis C among adults.|url=http://www.who.int/selection_medicines/committees/expert/19/applications/Pegyinterferon_6_4_3_A_Ad.pdf|website=who.int|accessdate=12 January 2017|page=11|deadurl=no|archiveurl=https://web.archive.org/web/20170113131153/http://www.who.int/selection_medicines/committees/expert/19/applications/Pegyinterferon_6_4_3_A_Ad.pdf|archivedate=13 January 2017|df=}}
5. ^1 2 3 {{cite web|title=Peginterferon alfa-2b (PegIntron) - Treatment - Hepatitis C Online|url=http://www.hepatitisc.uw.edu/page/treatment/drugs/peginterferon-alfa-2b-drug|website=www.hepatitisc.uw.edu|accessdate=12 January 2017|deadurl=no|archiveurl=https://web.archive.org/web/20161223193734/http://www.hepatitisc.uw.edu/page/treatment/drugs/peginterferon-alfa-2b-drug|archivedate=23 December 2016|df=}}
6. ^{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|page=639|edition=69}}
7. ^{{cite journal|title=Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance |vauthors=Ge D, Fellay J, Thompson AJ, etal |journal=Nature |year=2009 |volume=461|pages=399–401 |pmid=19684573 |doi=10.1038/nature08309|issue=7262}}
8. ^{{cite journal|title=Genetic variation in IL28B and spontaneous clearance of hepatitis C virus |vauthors=Thomas DL, Thio CL, Martin MP, etal |journal=Nature |year=2009 |pmid=19759533 |doi=10.1038/nature08463|volume=461|issue=7265|pages=798–801 |pmc=3172006}}
9. ^{{cite journal |vauthors=Ward AC, Touw I, Yoshimura A |title=The Jak-Stat pathway in normal and perturbed hematopoiesis |journal=Blood |volume=95 |issue=1 |pages=19–29 |date=January 2000 |pmid=10607680 |url=http://bloodjournal.hematologylibrary.org/cgi/pmidlookup?view=long&pmid=10607680}}
10. ^PATHWAYS :: IFN alpha
11. ^{{cite journal |vauthors=Thomas H, Foster G, Platis D |title=Corrigendum to ‘‘Mechanisms of action of interferon and nucleoside analogues’’ J Hepatol 39 (2003) S93–8 |journal=J Hepatol |volume=40 |issue=2 |pages=364 |date=February 2004 |doi=10.1016/j.jhep.2003.12.003 |url=http://www.journal-of-hepatology.eu/article/S0168-8278(03)00640-8/fulltext}}
12. ^{{cite journal |vauthors=Sangfelt O, Erickson S, Castro J, Heiden T, Einhorn S, Grandér D |title=Induction of apoptosis and inhibition of cell growth are independent responses to interferon-alpha in hematopoietic cell lines |journal=Cell Growth Differ. |volume=8 |issue=3 |pages=343–52 |date=March 1997 |pmid=9056677 |url=http://cgd.aacrjournals.org/cgi/content/abstract/8/3/343 |deadurl=no |archiveurl=https://web.archive.org/web/20140426201616/http://cgd.aacrjournals.org/cgi/content/abstract/8/3/343 |archivedate=2014-04-26 |df= }}
13. ^{{cite journal |vauthors=Thyrell L, Erickson S, Zhivotovsky B, etal |title=Mechanisms of Interferon-alpha induced apoptosis in malignant cells |journal=Oncogene |volume=21 |issue=8 |pages=1251–62 |date=February 2002 |pmid=11850845 |doi=10.1038/sj.onc.1205179 }}

External links

  • {{cite web |title=Peginterferon alfa-2b Approval Information |date=2009 |work=Drugs: Development & Approval Process |publisher=U.S. Food and Drug Administration |url=http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/ucm080727.htm}}
  • "Peg Intron Website"
  • {{cite news |title=Medicines patent loophole 'found' |newspaper=BBC News |date=2 January 2007 |url=http://news.bbc.co.uk/2/hi/health/6224601.stm}}
  • {{cite web |title=PEG-Intron (Peginterferon Alfa-2B) — Platelet Count Decreased — Suspected Cause — Side Effect Reports |publisher=DrugLib.com |url=http://www.druglib.com/adverse-reactions_side-effects/peg-intron/seriousness_death/reaction_platelet_count_decreased/ }}
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