title: The pharmacokinetics of oseltamivir and oseltamivir carboxylate in a critically ill pediatric patient receiving extracorporeal membrane oxygenation and continuous venovenous hemodialysis.
abstract: This report details the pharmacokinetics of oseltamivir and oseltamivir carboxylate following administration of high-dose oseltamivir in a critically ill child receiving extracorporeal membrane oxygenation (ECMO) and continuous venovenous hemodialysis (CVVHD). A 6-year-old critically ill male patient suffering from a presumed viral illness was transferred to our institution's pediatric intensive care unit from an outside hospital after developing respiratory failure and cardiomegaly. ECMO and oseltamivir therapy were initiated upon admission, and CVVHD was started on hospital day 3. Pharmacokinetic sampling occurred at an oseltamivir dose of approximately 4 mg/kg on hospital day 6. The patient's oseltamivir and oseltamivir carboxylate area under the plasma concentration time curves for the 12-hour dosing interval (AUC(0-12)) were 30.5 and 905 ng/mLhr, respectively. Drug clearance by CVVHD was 31.6 mL/min for oseltamivir and 26.9 mL/min for oseltamivir carboxylate. Pre- and postoxygenator oseltamivir and oseltamivir carboxylate plasma concentrations did not differ substantially. The patient's oseltamivir carboxylate plasma concentrations remained well above the reported mean 50% inhibitory concentration for 2009 pandemic H1N1 virus. However, despite receiving twice the standard dose of oseltamivir, the oseltamivir carboxylate AUC(0-12) in our patient was less than that reported in noncritically ill pediatric subjects. The reduced oseltamivir carboxylate AUC(0-12) found in our patient was most likely due to decreased drug absorption.
authors.affiliation: School of Pharmacy, University of Connecticut, Storrs, Connecticut  ; Renal Replacement Therapy Kinetics Study Group.
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Eyler
authors.forename: Kristin C
authors.initials: KC
authors.lastname: Klein
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Mueller
keywords: continuous renal replacement therapy; dialysis; extracorporeal membrane oxygenation; influenza; oseltamivir