Oseltamivir Pharmacokinetic Cohort Study

Oseltamivir treatment is currently the preferable treatment option in patients
infected with H1N1 influenza. Oseltamivir is an ester prodrug which is rapidly
hydrolysed by liver carboxylesterase to the active metabolite oseltamivir
carboxylate. Oseltamivir carboxylate is a selective neuramidase inhibitor of
influenza A and B. Oseltamivir and its hydrolysed carboxylate are almost fully
excreted renally by glomerular filtration and active tubular secretion. The
pharmacokinetics of oseltamivir in adults has been determined in several
studies. However, the pharmacokinetics in infected adults with significant
co-morbidities has not been studied, while these patients have an increased
risk for serious morbidity and even mortality when infected with influenza A or
B. Also, limited data is available regarding the pharmacokinetics of
oseltamivir in children and no data are available in children <3 months of age,
while these patients also have an increased risk for serious consequences of an
influenza infection. Currently, patients at risk are treated with oseltamivir,
according to national guidelines, while knowledge of the pharmacokinetic
properties of the drug is still limited.

Primary:
To determine the pharmacokinetics of oseltamivir in children and in adults with
significant co-morbidities

Secondary:
To examine whether the pharmacokinetics in our studied populations are
comparable with the PK in other populations
To examine the relationship between treatment related adverse events and plasma
drug levels and oropharyngeal viral load and plasma drug levels
To evaluate the specific influence of patient related parameters on
pharmacokinetic variability

Prospective cohort study

The sampling scheme of the oseltamivir pharmacokinetic cohort study will be
minimally invasive. If possible blood sampling will be carried out during
routine laboratory testing and will not require additional vena punctures.
However, in some cases this may be necessary.