Starflu Mechanism of Action

Pharmacology: 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.
The concentrations of oseltamivir carboxylate required for inhibition of influenza virus were highly variable depending on the assay method used and the virus tested. The 50% and 90% inhibitory concentrations (IC 50 and IC 90) were in the range of 0.0008 μM to >35μM and 0.004μM to > 100 μM, respectively (1 μM=0.284 μg/ml). The relationship between the in vitro antiviral activity in cell culture and the inhibition of influenza virus replication in humans has not been established.
Pharmacokinetics: Absorption: Oseltamivir is readily absorbed from the GIT after oral administration of oseltamivir phosphate (pro-drug) and is extensively converted by predominantly hepatic esterases to the metabolite (oseltamivir carboxylate). At least 75% of an oral dose reaches the systemic circulation as the metabolite. Exposure to the pro-drug is <5% relative to the active metabolite. Plasma concentrations of both pro-drug and active metabolite are proportional to dose and are unaffected by co-administration with food.
Distribution: The mean volume of distribution (Vss) of the active metabolite is approximately 23L in humans, a volume equivalent extracellular body fluid. Since neuraminidase activity is extracellular, oseltamivir carboxylate distributes to all sites of influenza virus spread. The binding of the oseltamivir carboxylate to human plasma protein is negligible (approximately 3%).
Metabolism: Oseltamivir is extensively converted to oseltamivir carboxylate by esterases located predominantly in the liver. In vitro studies demonstrated that neither oseltamivir nor the active metabolite is a substrate for, or an inhibitor of, the major cytochrome P450 isoforms. No phase 2 conjugates of either compound have been identified in vivo.
Elimination: Absorbed oseltamivir is primarily (>90%) eliminated by conversion to oseltamivir carboxylate. It is not further metabolised and is eliminated in the urine. Peak plasma concentrations of oseltamivir carboxylate decline with a half-life of 6-10 hours in most subjects. The active metabolite is eliminated entirely by renal excretion. Renal clearance (18.81/h) exceeds glomerular filtration rate (7.51/h) indicating that tubular secretion occurs in addition to glomerular filtration. Less than 20% of an oral radiolabelled dose is eliminated in faeces.