Осельтамивир

Использование

Oseltamivir is an orally active inhibitor of influenza virus neuraminidase; converted in vivo to the active acid metabolite. An antiviral drug. It is a COVID19-related research product.

Определение

ChEBI: A cyclohexenecarboxylate ester that is the ethyl ester of oseltamivir acid. An antiviral prodrug (it is hydrolysed to the active free carboxylic acid in the liver), it is used to slow the spread of influenza.

Показания

Oseltamivir phosphate (Tamiflu) is the ethyl ester prodrug of oseltamivir carboxylate, an analogue of neuraminic (sialic) acid that is a reversible competitive antagonist of influenza A and B neuraminidase.Influenza virus resistant to oseltamivir has not been found in naturally acquired isolates but has been isolated from influenza patients who have undergone treatment with this drug.These resistant strains contain mutations in the active site of neuraminidase and are generally less virulent and infective than nonresistant virus. In vitro passage of influenza virus in the presence of oseltamivir carboxylate can produce mutations in hemagglutinin that decrease the overall dependence of viral replication on neuraminidase; however, the clinical relevance of this resistance mechanism is unknown.

Антимикробная активность

Oseltamivir is active against influenza A and B, but no other virus.

Приобретенная устойчивость

Mutations in the neuraminidase (H274Y) have been detected in treated patients with seasonal H1N1 infection. Cross-resistance with zanamivir has been described in vitro.

Фармацевтические приложения

A selective neuraminidase inhibitor, formulated as the phosphate salt of the ethyl ester for oral administration.

Фармакокине?тика

Oral absorption: c. 75%
C_max 75 mg oral: 0.35–0.55 mg/L after 4 h
Plasma half-life: 7–9 h
Plasma protein binding: Not known
The ethyl ester prodrug is hydrolyzed by hepatic esterases to release the active compound, oseltamivir carboxylate. Drug is excreted in the urine as the carboxylate derivative.

Клиническое использование

Oseltamivir is approved for the treatment of uncomplicated acute influenza in patients aged 1 year and older. It decreases the duration of illness by 1 to 1.5 days when treatment is initiated within 48 hours of the onset of symptoms. Oseltamivir is also indicated for the prophylaxis of influenza in individuals aged 13 and older. It reduces infection rates to approximately 10 to 25% of that found in untreated populations; however, it is not intended to substitute for the early vaccination recommended by the CDC. Oseltamivir can be used as postexposure prophylaxis in household contacts of infected patients, with infection rates of treated patients around 10% of placebo control levels.

Побочные эффекты

The most frequently reported adverse effects of oseltamivir are nausea and vomiting.These events are usually mild to moderate, occur during the first 1 to 2 days of treatment, and can be lessened by taking the drug with food. Bronchitis, insomnia, and vertigo may also occur. Oseltamivir may not be indicated for use in certain individuals. Its efficacy in patients with chronic cardiac or respiratory disease has not been established. In clinical trials, no difference in the incidence of complications was seen between treatment and control groups. The efficacy of oseltamivir has not been demonstrated in immunocompromised patients, patients who begin treatment after 40 hours of symptoms, or patients given repeated prophylactic courses of therapy. Dosage adjustment is recommended for individuals with renal insufficiency; the drug’s safety in patients with hepatic insufficiency is unknown.