title: Pharmacokinetics of oseltamivir and oseltamivir carboxylate in critically ill patients receiving continuous venovenous hemodialysis and/or extracorporeal membrane oxygenation.
abstract: 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).
  
  
  METHODS
  Prospective, open-label, pharmacokinetic study.
  
  
  METHODS
  Intensive care units of an academic medical center.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA. rachel.eyler@uconn.edu
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Eyler
authors.forename: Michael
authors.initials: M
authors.lastname: Heung
authors.forename: Melissa
authors.initials: M
authors.lastname: Pleva
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Sowinski
authors.forename: Pauline K
authors.initials: PK
authors.lastname: Park
authors.forename: Lena M
authors.initials: LM
authors.lastname: Napolitano
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Mueller
mesh_terms: D000046:Academic Medical Centers; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016638:Critical Illness; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011446:Prospective Studies; D006435:Renal Dialysis; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; C535162:oseltamivir carboxylate