| Indication |
Oseltamivir (Tamiflu) is for the treatment of uncomplicated acute
illness due to influenza infection in patients 1 year and older who have
been symptomatic for no more than 2 days. It is also used for the
prophylaxis of influenza in adult patients and adolescents 13 years and
older. |
| Pharmacodynamics |
Oseltamivir is an antiviral drug, a neuraminidase inhibitor used
in the treatment and prophylaxis of both influenza A and influenza B.
Oseltamivir is a prodrug (usually administered as phosphate), it is
hydrolysed hepatically to the active metabolite, the free carboxylate of
oseltamivir (GS4071). Like zanamivir, oseltamivir acts as a
transition-state analogue inhibitor of influenza neuraminidase. |
| Mechanism of action |
Oseltamivir is an ethyl ester prodrug requiring ester hydrolysis
for conversion to the active form, oseltamivir carboxylate. The proposed
mechanism of action of oseltamivir is inhibition of influenza virus
neuraminidase with the possibility of alteration of virus particle
aggregation and release. |
| Absorption |
Readily absorbed from the gastrointestinal tract after oral administration with a bioavailability of 75%. |
| Volume of distribution |
|
| Protein binding |
Oseltamivir carboxylate: low (3%), Oseltamivir free base: 42%. |
| Metabolism |
Extensively converted to oseltamivir carboxylate by esterases
located predominantly in the liver. Neither oseltamivir nor oseltamivir
carboxylate is a substrate for, or inhibitor of, cytochrome P450
isoforms. At least 75% of an oral dose reaches the systemic circulation
as oseltamivir carboxylate. |
| Route of elimination |
Absorbed oseltamivir is primarily (>90%) eliminated by
conversion to oseltamivir carboxylate. Oseltamivir carboxylate is not
further metabolized and is eliminated in the urine. Oseltamivir
carboxylate is eliminated entirely (>99%) by renal excretion. |
| Half life |
1 to 3 hours in most subjects after oral administration. |
| Clearance |
Not Available |
| Toxicity |
At present, there has been no experience with overdose. Single
doses of up to 1000 mg of oseltamivir have been associated with nausea
and/or vomiting. Mean LD (intravenous, mouse) = 100 mg/kg. |
