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Fomivirsen

Fomivirsen Struktur
144245-52-3
CAS-Nr.
144245-52-3
Englisch Name:
Fomivirsen
Synonyma:
Isis 2922;Fomivirsen
CBNumber:
CB61074682
Summenformel:
C204H263N63O114P20S20
Molgewicht:
6682.45
MOL-Datei:
144245-52-3.mol

Fomivirsen Eigenschaften

storage temp. 
Store at -20°C

Sicherheit

Fomivirsen Chemische Eigenschaften,Einsatz,Produktion Methoden

Indications

Fomivirsen (Vitravene), an anti-CMV agent, is the first antisense oligonucleotide to be approved by the U. S. Food and Drug Administration (FDA) as an antiviral therapy. Fomivirsen is an oligonucleotide complementary to the major immediate early region 2 (IE2) of CMV mRNA. By binding to IE2 mRNA, fomivirsen prevents its translation to protein and thereby blocks viral replication. Because this mechanism of action is different from that of other antiviral agents, crossresistance with other drugs used to treat CMV is unlikely.

Pharmazeutische Anwendungen

An antisense oligonucleotide, 21 bases in length, representing the mirror image of a region of mRNA coding for a regulatory protein of CMV. It is administered as the sodium salt by intraocular injection. Experiments in monkeys suggest that it has a very long elimination half-life (c. 3 days). Because of its unique mode of action fomivirsen retains activity against strains of CMV resistant to other antiviral agents. Side effects commonly include ocular inflammation, which is responsive to topical steroids, and raised intraocular pressure.

Mechanism of action

Fomivirsen inhibits CMV by at least two mechanisms. The first is a sequence-specific antisense binding to inhibit expression of immediate-early genes, thus preventing viral replication. The second is sequence-independent and involves inhibition of adsorption of CMV to host cells, probably by direct binding to viral coat proteins. The reduction of immediate-early protein synthesis occurs in a dose-dependent manner. Although it does inhibit viral replication, fomivirsen does not eradicate the virus whose DNA, as for all herpesviruses, is integrated into the human genome. Therefore, treatment will have to continue for the life of the patient.

Pharmakokinetik

The series of clinical trials that led to approval by the U.S. Food and Drug Administration involved 430 eyes in 330 patients. Fomivirsen significantly delayed progression of CMV retinitis in patients with AIDS, including those who had failed treatment with ganciclovir or foscarnet, the first-line therapies. Fomivirsen is administered by intravitreal injection at doses of 165 μg once weekly for three weeks of induction and then once every two weeks. It also can be administered in a dose of 330 μg on days 1 and 15 and then once a month thereafter. Mean maximum retinal concentrations of fomivirsen occur at 2 days, and the elimination half-life after a single, 115-μg dose in monkey retina was 78 hours. There are no systemic side effects. Ocular side effects include increased intraocular pressure and mild to moderate intraocular inflammation that can be reversed with topical steroid treatment. It is important that side effects be minor, because treatment will be lifelong.

Clinical Use

Fomivirsen is used to treat CMV retinitis in patients with AIDS who have not responded to other treatments or in whom other treatments are contraindicated. It appears to be at least as effective as other treatments and produces fewer side effects. Because CMV retinitis is often associated with CMV infection elsewhere in the body, patients undergoing treatment with fomivirsen should be monitored for extraocular CMV disease.

Nebenwirkungen

Iritis, which affects up to 25% of patients undergoing fomivirsen therapy, can be managed with topical corticosteroids. Vitreitis and increased intraocular pressure may also result from fomivirsen administration. Fomivirsen is contraindicated in patients who have been treated with cidofovir within the previous 2 to 4 weeks because cidofovir increases the risk of ocular inflammation.

Fomivirsen Upstream-Materialien And Downstream Produkte

Upstream-Materialien

Downstream Produkte


Fomivirsen Anbieter Lieferant Produzent Hersteller Vertrieb H?ndler.

Global( 7)Lieferanten
Firmenname Telefon E-Mail Land Produktkatalog Edge Rate
QUALITY CONTROL SOLUTIONS LTD. 0755-66853366; 13670046396
ORDERS@QCSRM.COM China 24342 58
Nugene Biopharm Science (Hangzhou) Co., Ltd. 13326014885
service@nugene.com.cn China 55 58

  • Fomivirsen
  • Isis 2922
  • 144245-52-3
  • C204H263N63O114P20S20
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