Definition
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.
Originator
Tamiflu,Hoffmann-La Roche Inc
Uses
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.
Therapeutic Function
Antiviral
Antimicrobial activity
Oseltamivir is active against influenza A and B, but no other
virus.
Acquired resistance
Mutations in the neuraminidase (H274Y) have been
detected in treated patients with seasonal H1N1 infection.
Cross-resistance with zanamivir has been described in
vitro.
Pharmaceutical Applications
A selective neuraminidase inhibitor, formulated as the phosphate
salt of the ethyl ester for oral administration.
Pharmacokinetics
Oral absorption: c. 75%
Cmax 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.
Clinical Use
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.
Clinical Use
Treatment and prevention of susceptible influenza A (H3N2) and B
infections in adults and young children
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
Oseltamivir is a prodrug; it is extensively metabolised by
esterases in the liver to the active carboxylate metabolite.
Oseltamivir carboxylate is not further metabolised and
is eliminated entirely by renal excretion. Renal clearance
exceeds glomerular filtration rate indicating that tubular
secretion occurs in addition to glomerular filtration. Less
than 20% of an oral radiolabelled dose is eliminated in
faeces.