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Encyclopedia > Zanamivir
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Molecular structure of zanamivir
Zanamivir Jump to: navigation, search Image File history File links Zanamivir. ...

5-(acetylamino)-4-[(aminoiminomethyl)amino]- 2,6-anhydro-3,4,5-trideoxy- D-glycero-D-galacto-non-2-enonic acid

Empirical formula C12H20N4O7
Molecular weight 332.3
Bioavailability (Oral) 2%
Metabolism excreted unchanged
Half life (Inhaled) 2.5-5.1 hours
Excretion renal
Pregnancy category B1 (Australia)

Zanamivir is a neuraminidase inhibitor used in the treatment of and prophylaxis of both influenza A and influenza B. Zanamivir was the first neuraminidase inhibitor commercially developed. It is currently marketed by GlaxoSmithKline under the trade name Relenza®. The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Jump to: navigation, search The half-life of a radioactive substance is the time required for half of a sample to undergo radioactive decay. ... Jump to: navigation, search Excretion is the biological process by which an organism chemically separates waste products from its body. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother. ... Neuraminidase inhibitors are a class of antiviral drugs, whose mode of action relies on blocking the function of viral neuraminidase protein, thus preventing the virus from budding from the host cell. ... Jump to: navigation, search Negatively stained flu virions. ... GlaxoSmithKline (GSK) plc is a pharmaceutical, biologicals, and healthcare company. ... A trade name, also known as a trading name or a business name, is the legal name of a business, or the name which a business trades under for commercial purposes. ...

Contents


Development

Zanamivir was discovered in 1989 by scientists at the Australian biotechnology company Biota Holdings, working in conjunction with the CSIRO and the Victorian College of Pharmacy. The development was part of Biota's ongoing program to develop antiviral agents through rational drug design. An outline of the successful rational design strategy used was published in a paper in Nature (von Itzstein et al., 1993). The Commonwealth Scientific and Industrial Research Organisation (CSIRO) is the national government body for scientific research in Australia. ... Nature is one of the oldest and most reputable general-purpose scientific journals, first published on November 4, 1869. ...


The strategy relied on the availability of the crystal structure of influenza neuraminidase which was achieved by x-ray crystallography. It was known as far back as 1974 that 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA), a sialic acid analogue, was an inhibitor of neuraminidase (Meindl et al., 1974). Using the crystal structure of neuraminidase and DANA as a starting point, the researchers employed a computer-aided process to attempt to design a molecule which better fitted (and therefore inhibited) the active site of neuraminidase. Zanamivir, a transition-state analogue inhibitor of neuraminidase, was the result. Jump to: navigation, search Neuraminidase ribbon diagram Neuraminidase is an antigenic glycoprotein enzyme (EC 3. ... X-ray crystallography is a technique in crystallography in which the pattern produced by the diffraction of X-rays through the closely spaced lattice of atoms in a crystal is recorded and then analyzed to reveal the nature of that lattice. ... Sialic acid Sialic acid is a derivative of a nine-carbon monosaccharide, named from the Greek σιαλοσ (sialos) saliva. It is the negative charge of this chemical that is responsible for the slippery feel of saliva and mucins coating the body’s organs. ...


In 1990, zanamivir was licensed to Glaxo (now GlaxoSmithKline) for exclusive worldwide development and marketing. In 1999, the product was approved for marketing in the US and subsequently has been registered by GSK in a total of 70 countries. GlaxoSmithKline (GSK) plc is a pharmaceutical, biologicals, and healthcare company. ...


Limitations

Whilst zanamivir proved to be a potent and effective inhibitor of influenza neuraminidase and inhibitor of influenza virus replication in vitro and in vivo, this didn't necessarily translate into a successful clinical treatment for influenza. In clinical trials it was found that zanamivir was able to reduce the time to symptom resolution by 1.5 days provided therapy was started within 48 hours of the onset of symptoms.


A further limitation concerns the poor oral bioavailability of zanamivir. This meant that oral dosing was impossible limiting dosing to the parenteral routes. Zanamivir, therefore, is administered by inhalation - a route that was chosen for patient compliance with therapy. But even this route of administration is not acceptable to many in the community. In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ...


A troubled commercial venture

Biota, being only a small company, was not able to bring the drug to market by itself. Consequently, it was licensed to Glaxo (now GlaxoSmithKline) to complete development and to market internationally as Relenza, delivered via Glaxo's proprietary, and some would say cumbersome, Diskhaler inhalation device. The license agreement entitled Biota to receive a 7% royalty on Glaxo's sales of Relenza. GlaxoSmithKline (GSK) plc is a pharmaceutical, biologicals, and healthcare company. ...


A combination of factors has resulted in the limited commercial success of zanamivir (Relenza). The relatively small effect on the timecourse of influenza symptoms, the inhalation dosage form, a less-than-ideal device, and high expense make it a difficult product to market well. And although zanamivir was the first neuraminidase inhibitor to the market, it had only a few months lead over the second entrant, oseltamivir (Tamiflu), with an oral formulation much preferred by patients. Faced with this competition, GSK effectively abandoned the product. Neuraminidase inhibitors are a class of antiviral drugs, whose mode of action relies on blocking the function of viral neuraminidase protein, thus preventing the virus from budding from the host cell. ... Jump to: navigation, search Oseltamivir is an antiviral drug, a neuraminidase inhibitor used in the treatment and prophylaxis of both influenza A and influenza B. Oseltamivir was the first orally active neuraminidase inhibitor commercially developed. ...


When first marketed in 1999/00, Relenza captured close to 50% of the global market for neuraminidase inhibitors. But after the launch year, GSK cut virtually all promotion and other support for Relenza, allowing the product's sales and market share to slide in every major market over the following four years. By 2004 Relenza held only a 3% share of the estimated US$330 million global market.


In May 2004, Biota issued a writ against GSK for failing to support and promote Relenza. The writ claimed that GSK was in breach of several obligations:

  • GSK restricted Relenza to its proprietary Diskhaler system, and did not adequately pursue alternative or improved inhalation systems.
  • GSK withdrew support for crucial post-approval clinical studies designed to expand the product's use and market acceptance.
  • After the launch year, GSK failed to properly launch Relenza in a number of countries where the product was registered, and allowed registrations to be stopped, cancelled or scheduled for cancellation.
  • After the launch year, GSK withdrew promotion support for Relenza, allowing the sales and market share to decline in all key markets, even in those markets where there was no direct competition.

A prototype for others

Zanamivir was the first of the neuraminidase inhibitors. Despite the limited commercial success of this drug, the work and strategies employed in the development of zanamivir were important first-steps in the development of further members of this class including oseltamivir and the candidate drug RWJ-270201 (Phase I trials). As a result more effective and potent treatments for influenza may be developed in the future. Neuraminidase inhibitors are a class of antiviral drugs, whose mode of action relies on blocking the function of viral neuraminidase protein, thus preventing the virus from budding from the host cell. ... Jump to: navigation, search Oseltamivir is an antiviral drug, a neuraminidase inhibitor used in the treatment and prophylaxis of both influenza A and influenza B. Oseltamivir was the first orally active neuraminidase inhibitor commercially developed. ...


References

  • Meindl P, Bodo G, Palese P, Schulman J, Tuppy H (1974). Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid. Virology 58 (2), 457-463.
  • von Itzstein M, Wu W-Y, Kok GB, Pegg MS, Dyason JC, Jin B, Phan TV, Smythe ML, White HF, Oliver SW, et al. (1993). Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 363 (6428), 418-423.


Antivirals edit
Antiherpesvirus agents edit

{Acyclovir} {Cidofovir} {Docosanol} {Famciclovir} {Foscarnet} {Fomivirsen} {Ganciclovir} {Idoxuridine} {Penciclovir} {Trifluridine} {Valaciclovir} {Valganciclovir} {Vidarabine} Wikipedia does not yet have an article with this exact name. ... Aciclovir (INN) or aciclovir (USAN), marketed as Zovirax®, is one of the main antiviral drugs. ... Jump to: navigation, search Chemical structure of cidofovir Cidofovir is an injectable antiviral medication for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. It suppresses CMV replication by selective inhibition of viral DNA synthesis. ... Jump to: navigation, search Docosanol 10% cream is a topical treatment for recurrent herpes simplex labialis episodes (episodes of cold sores or fever blisters). ... Ganciclovir sodium (Cytovene®) is an antiviral medication used to treat cytomegalovirus (CMV) infections. ... Jump to: navigation, search Valaciclovir (INN) or valacyclovir (USAN) is an antiviral drug used in the management of herpes simplex. ... Jump to: navigation, search Valganciclovir hydrochloride (Valcyte®) is an antiviral medication used to treat cytomegalovirus infections. ... Jump to: navigation, search Chemical structure of vidarabine Vidarabine is an anti-viral drug which is active against herpes simplex and varicella zoster viruses. ...

Antiinfluenza agents [ ]

{Amantadine} {Oseltamivir} {Rimantidine} {Zanamivir} Jump to: navigation, search Antiviral drugs are a class of medication used specifically for treating viral infections. ... Jump to: navigation, search Amantadine, 1-aminoadamantane, is an antiviral drug that was approved by the FDA in 1976 for the treatment of influenza type A in adults. ... Jump to: navigation, search Oseltamivir is an antiviral drug, a neuraminidase inhibitor used in the treatment and prophylaxis of both influenza A and influenza B. Oseltamivir was the first orally active neuraminidase inhibitor commercially developed. ...


Antiretrovirals edit

NRTIs edit Jump to: navigation, search Antiretroviral drugs are medications for the treatment of infection by the retrovirus HIV. Different antiretroviral drugs act at various stages of the HIV life cycle. ... Jump to: navigation, search Antiretroviral drugs are medications for the treatment of infection by the retrovirus HIV. Different antiretroviral drugs act at various stages of the HIV life cycle. ...

{Zidovudine} {Didanosine} {Stavudine} {Zalcitabine} {Lamivudine} {Abacavir} Zidovudine (INN) or azidothymidine (abbreviated to AZT) is an antiretroviral drug, the first antiviral treatment to be approved for use against HIV. It is also sold under the names Retrovir and Retrovis, and as an ingredient in Combivir and Trizivir. ... Jump to: navigation, search Didanosine (2-3-dideoxyinosine, ddI, Videx®) differs from other nucleoside analogues, because it does not have any of the regular bases, instead it has hypoxanthine attached to the sugar ring. ... Jump to: navigation, search Stavudine (2-3-didehydro-2-3-dideoxythymidine, d4T, brand name Zerit®) is a thymidine analogue active against HIV. It is phosphorylated by cellular kinases into active triphosphate. ... Jump to: navigation, search Zalcitabine (2-3-dideoxycytidine, ddC), is a derivative of the naturally existing deoxycytidine, made by replacing the hydroxyl group in position 3 with a hydrogen. ... Lamivudine(2-3-dideoxy-3-thiacytidine, 3TC) is a potent reverse transcriptase inhibitor. ... Jump to: navigation, search Abacavir (ABC) is extremely potent reverse transcriptase inhibitor, meant for the treatment of AIDS. ABC is capable of crossing the blood-brain barrier. ...


NNRTIs edit Jump to: navigation, search Antiretroviral drugs are medications for the treatment of infection by the retrovirus HIV. Different antiretroviral drugs act at various stages of the HIV life cycle. ...

{Nevirapine} {Efavirenz} {Delavirdine} Jump to: navigation, search Nevirapine is a controversial AIDS drug. ... DESCRIPTION SUSTIVA® (efavirenz) is a human immunodeficiency virus type 1 (HIV-1) specific, non-nucleoside, reverse transcriptase inhibitor (NNRTI). ...


PIs edit Jump to: navigation, search Antiretroviral drugs are medications for the treatment of infection by the retrovirus HIV. Different antiretroviral drugs act at various stages of the HIV life cycle. ...

{Saquinavir} {Indinavir} {Atazanavir} {Ritonavir} {Nelfinavir} {Amprenavir} {Lopinavir} Saquinavir (Fortovase®, Roche) is a protease inhibitor, used as a component of HIV therapy. ... Categories: Stub ... Ritonavir is a drug from the protease inhibitor class used to treat AIDS. It is manufactured as Norvir® by Abbott Laboratories. ... Jump to: navigation, search Nelfinavir (Viracept®) is an antitretroviral drug used in the treatment of the human immunodeficiency virus (HIV). ...


Other antiviral agents edit

{Fomivirsen} {Imiquimod} {Interferon} {Lamivudine} {Ribavirin} Jump to: navigation, search Antiviral drugs are a class of medication used specifically for treating viral infections. ... Jump to: navigation, search Interferons (IFNs) are natural proteins produced by the cells of the immune systems of most animals in response to challenges by foreign agents such as viruses, bacteria, parasites and tumor cells. ... Lamivudine(2-3-dideoxy-3-thiacytidine, 3TC) is a potent reverse transcriptase inhibitor. ... Ribavirin (Copegus®; Rebetol®) is an anti-viral drug active against a number of DNA and RNA viruses. ...


  Results from FactBites:
 
zanamivir - Medical and health information on the common cold and flu (480 words)
DRUG CLASS AND MECHANISM: Zanamivir is a neuraminidase inhibitor that prevents the spread of influenza A and B viruses, the viruses responsible for the "flu." Neuraminidase is an enzyme that is required by the influenza viruses to spread from infected cells to healthy cells.
Zanamivir blocks the action of neuraminidase thereby reducing the spread of influenza.
Zanamivir does not interact with the flu vaccine.
Relenza Online, Description, Chemistry, Ingredients - Zanamivir - RxList Monographs (720 words)
Zanamivir is a white to off-white powder with a solubility of approximately 18 mg/mL in water at 20
Antiviral Activity: The antiviral activity of zanamivir against laboratory and clinical isolates of influenza virus was determined in cell culture assays.
The concentrations of zanamivir required for inhibition of influenza virus were highly variable depending on the assay method used and virus isolate tested.
  More results at FactBites »

 
 

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