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| Primary information |
|---|
| ID | 10135 |
| Therapeutic ID | Th1019 |
| Protein Name | Peginterferon alfa-2b |
| Sequence | >Th1019_Peginterferon_alfa-2b
CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE
|
| Molecular Weight | 31000 |
| Chemical Formula | C130H219N43O42 |
| Isoelectric Point | 5.99 |
| Hydrophobicity | NA |
| Melting point | 61 |
| Half-life | Approximately 40 hours (range 22 to 60 hours) in patients with HCV infection |
| Description | Peginterferon alfa-2b is a covalent conjugate of recombinant alfa-2b interferon with monomethoxy polyethylene glycol (PEG). The average molecular weight of the PEG portion of the molecule is 12,000 daltons. The average molecular weight of the PEG-Intron molecule is approximately 31,000 daltons. The specific activity of peginterferon alfa-2b is approximately 0.7 x 108 IU/mg protein. Interferon alfa-2b is a water-soluble protein with a molecular weight of 19,271 daltons produced by recombinant DNA techniques. It is obtained from the bacterial fermentation of a strain of Escherichia coli bearing a genetically engineered plasmid containing an interferon gene from human leukocytes. The PEG strand protects the molecule in vivo from proteolytic breakdown, substantially increases its in vivo half-life, and reduces immunogenicity by wrapping around and physically hindering access to the protein portion of the molecule. |
| Indication/Disease | Used for the treatment of chronic hepatitis C in patients not previously treated with interferon alpha who have compensated liver disease and are at least 18 years of age. |
| Pharmacodynamics | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2-5 oligoadenylate synthetase (2-5 A synthetase) and protein kinase R. |
| Mechanism of Action | It binds to type I interferon receptors IFNAR1 and IFNAR2c which upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. |
| Toxicity | NA |
| Metabolism | NA |
| Absorption | After a single subcutaneous dose of peginterferon alfa-2b, the mean absorption half-life was 4.6 hours. |
| NA |
| Clearance | Oral cl=22 mL/hr/kg [patients with HCV infection], Renal elimination accounts for 30% of the clearance. |
| Categories | Adjuvants, Immunologic, Alcohols, Alfa Interferons, Amino Acids, Peptides, and Proteins, Anti-Infective Agents, Antineoplastic and Immunomodulating Agents, Antiviral Agents, Biological Factors, Cancer immunotherapy, Compounds used in a research, industrial, or household setting, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 CYP1A2 Inhibitors (strength unknown), Cytochrome P-450 CYP2C9 Inducers, Cytochrome P-450 CYP2C9 Inducers (weak), Cytochrome P-450 CYP2D6 Inhibitors, Cytochrome P-450 CYP2D6 Inhibitors (weak), Cytochrome P-450 Enzyme Inducers, Cytochrome P-450 Enzyme Inhibitors, Cytokines, Drug Carriers, Ethylene Glycols, Glycols, Hepatitis C, Immunosuppressive Agents, Immunotherapy, Intercellular Signaling Peptides and Proteins, Interferon alpha, Interferon Type I, Interferon-alpha, Interferons, Macromolecular Substances, Myelosuppressive Agents, Pegylated agents, Peptides, Polymers, Proteins, Treatments for Hepatitis C |
| Patents Number | CA1341567 |
| Date of Issue | 19-Feb-2008 |
| Date of Expiry | 19-Feb-2025 |
| Drug Interaction | Aminophylline. Interferon increases the effect and toxicity of theophylline |
| Target | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 |
| Brand Name | PEG-Intron |
| Company | Schering Corp |
| Brand Description | Schering Corp |
| Prescribed For | Used to treat chronic hepatitis C in adults. Peginterferon alfa-2b is often used in combination with another medication called ribavirin (Rebetol, Ribasphere) to treat hepatitis C in adults and children who are at least 3 years old. It may be used in comb |
| Chemical Name | NA |
| Formulation | Provided in both vials and the REDIPEN. Each vial contains either 74 mcg, 118.4 mcg, 177.6 mcg, or 222 mcg of PegIntron as a white to off-white tablet-like solid that is whole/in pieces or as a loose powder, and 1.11 mg dibasic sodium phosphate anhydrous, |
| Physical Appearance | Powder |
| Route of Administration | Subcutaneous Injection |
| Recommended Dosage | 1.5 mcg/kg/week. The volume of PegIntron to be injected depends on the strength of PegIntron and patient's body weight |
| Contraindication | Allergic or in case of having autoimmune hepatitis, liver failure, severe kidney disease, a hemoglobin blood cell disorder |
| Side Effects | Vision problems; fast heart rate, feeling like you might pass out; unusual weakness; high fever with severe stomach pain and bloody diarrhea; pain or burning when you urinate; severe pain in your upper stomach spreading to your back, nausea and vomiting and new or worsening liver symptoms. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |