STUDY OBJECTIVE: To investigate oseltamivir and oseltamivir carboxylate 
pharmacokinetics in critically ill patients who were receiving continuous 
venovenous hemodialysis (CVVHD) and/or extracorporeal membrane oxygenation 
(ECMO).
DESIGN: Prospective, open-label, pharmacokinetic study.
SETTING: Intensive care units of an academic medical center.
PATIENTS: Thirteen critically ill patients aged 13 years or older with suspected 
or confirmed H1N1 influenza who had a prescription for oseltamivir and were 
concurrently receiving CVVHD and/or ECMO between October 2009 and January 2010.
INTERVENTION: Oseltamivir 150 mg was administered nasogastrically or 
nasoenterically every 12 hours. Blood samples were collected at baseline and at 
1, 2, 4, 6, 8, 10, and 12 hours after administration of the fourth oseltamivir 
dose or subsequent doses. In patients receiving CVVHD, effluent also was 
collected at the same time points. Urine was collected throughout the 12-hour 
dosing interval.
MEASUREMENTS AND MAIN RESULTS: Eight patients received CVVHD only, four patients 
received both CVVHD and ECMO, and one patient received ECMO only. 
Pharmacokinetic parameters for the patient who received only ECMO were not 
reported. The median maximum plasma concentration and area under the plasma 
concentration-time curve for the 12-hour dosing interval (AUC(0-12) ) for the 
remaining 12 patients were 83.4 ng/ml and 216 ng•hour/ml, respectively, for 
oseltamivir and 2000 ng/ml and 21,500 ng•hour/ml, respectively, for oseltamivir 
carboxylate. Mean clearance due to CVVHD was 33.8 ml/minute for oseltamivir and 
50.2 ml/minute for oseltamivir carboxylate. For patients who received ECMO, no 
substantial differences between pre- and post-ECMO oxygenator plasma 
concentrations were found for oseltamivir or oseltamivir carboxylate.
CONCLUSION: Although the optimal pharmacokinetic-pharmacodynamic targets for 
oseltamivir carboxylate remain unclear, in the patients receiving CVVHD with or 
without ECMO, a regimen of oseltamivir 150 mg every 12 hours yielded a median 
oseltamivir carboxylate AUC(0-12) considerably higher than would be expected in 
non-critically ill patients receiving the same dosage regimen.