Interferon alfacon-1

Synonyms :
CIFN, consensus interferon, IFN Alfacon-1, Interferon Consensus, Methionyl, methionyl interferon consensus, methionyl-interferon-consensus, rCon-IFN, Recombinant Consensus Interferon, Recombinant methionyl human consensus interferon

Status : approved

Category

Antiviral Agents

Therapeutic Classification

IMMUNOSTIMULANTS

ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSTIMULANTS
IMMUNOSTIMULANTS
Immunosuppressive Agents

Description

Interferon alfacon-1 is a recombinant non-naturally occurring type-I interferon. The 166-amino acid sequence of Interferon alfacon-1 was derived by scanning the sequences of several natural interferon alpha subtypes and assigning the most frequently observed amino acid in each corresponding position. Four additional amino acid changes were made to facilitate the molecular construction, and a corresponding synthetic DNA sequence was constructed using chemical synthesis methodology. Interferon alfacon-1 differs from interferon alfa-2b at 20/166 amino acids (88% homology), and comparison with interferon-beta shows identity at over 30% of the amino acid positions. Interferon alfacon-1 is produced in Escherichia coli (E. coli) cells that have been genetically altered by insertion of a synthetically constructed sequence that codes for Interferon alfacon-1. Prior to final purification, Interferon alfacon-1 is allowed to oxidize to its native state, and its final purity is achieved by sequential passage over a series of chromatography columns. This protein has a molecular weight of 19,434 daltons.

Used

For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi’s sarcoma

Mechanism Of Action

Interferon alpha 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. The resulting actions include gene transcription, inhibition of cellular growth, alteration of the state of cellular differentiation, interference with oncogene expression, alteration of cell surface antigen expression, increasing phagocytic activity of macrophages, and augmentation of the cytotoxicity of lymphocytes for target cells.

Dosage

Form Route Strength
Solution subcutaneous 0.03 mg

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.

Toxic Effect

Reproductive toxicity studies in pregnant rhesus monkeys and golden Syrian hamsters demonstrated an increase in fetal loss in hamsters treated with Interferon alfacon-1 at doses of > 150 mcg/kg/day, and in rhesus monkeys at doses of 3 and 10 mcg/kg/day. The Interferon alfacon-1 toxicity profile described is consistent with the known toxicity profile of other alpha interferons.

Absorption

Subcutaneous bioavailability averages 99% in golden Syrian hamsters and 83% to 104% in rhesus monkeys.

Half Life

The terminal half-life following subcutaneous dosing was 1.3 hours in golden Syrian hamsters and 3.4 hours in rhesus monkeys.

Elimination Route

Due predominantly to catabolism and excretion by the kidneys.

Clearance

Clearance, averaging 1.99 mL/minute/kg in golden Syrian hamsters and 0.71 to 0.92 mL/minute/kg in rhesus monkeys

Chemical Classification

Peptides

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

Chemical Name

CIFN

Brands

name Dosage form Country
Infergen solution Canada

Drug Drug Interactions

  •  Aldesleukin  : Interferons (Alfa) may enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination.
  •  Clozapine  : Myelosuppressive Agents may enhance the adverse/toxic effect of Clozapine. Specifically, the risk for agranulocytosis may be increased.
  •  Metamizole  : May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
  •  Methadone  : Interferons (Alfa) may increase the serum concentration of Methadone.
  •  Ribavirin  : Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin. Hemolytic anemia has been observed.
  •  Zidovudine  : Interferons may enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine.

Calculated Property

kind Value Source

Affected organism

Humans and other mammals

Target within organism

  • Interferon alpha/beta receptor 1 : in Human
  • Interferon alpha/beta receptor 2 : in Human