title: Impact of extracorporeal membrane oxygenation and continuous venovenous hemodiafiltration on the pharmacokinetics of oseltamivir carboxylate in critically ill patients with pandemic (H1N1) influenza.
abstract: OBJECTIVE
  The neuraminidase inhibitor oseltamivir is a recommended treatment for influenza A (H1N1) infection. In rare cases, some patients develop influenza-associated multiple organ failures, requiring rescue therapies such as extracorporeal membrane oxygenation (ECMO) or continuous venovenous hemodiafiltration (CVVHDF). This study was designed to evaluate the impact of ECMO and CVVHDF on the pharmacokinetics of oseltamivir carboxylate (OC) in critically ill patients with pandemic (H1N1) influenza treated with oseltamivir.
  
  
  METHODS
  Seven critically ill patients on venovenous ECMO for severe pandemic (H1N1) influenza associated with acute respiratory distress syndrome were treated with various doses of oseltamivir (75 or 150 mg twice daily). Because of acute kidney injury, 3 of them also received CVVHDF. OC, the active form of oseltamivir, was quantified in plasma, and main pharmacokinetic parameters were determined.
  
  
  RESULTS
  OC Cmax (1029 ± 478 ng/mL) and area under the curve (9.00 ± 4.52 mcg·h/mL) for patients on ECMO with preserved renal function were comparable with those of healthy volunteers or noncritically ill patients. Patients both on ECMO and CVVHDF had 4-to 5-fold higher OC Cmax and area under the curve.
  
  
  CONCLUSIONS
  ECMO by itself did not impact on the pharmacokinetics of OC. However, the drug accumulated in the plasma of patients on ECMO who also received CVVHDF for renal failure. Based on these results, we recommend that oseltamivir dosage should be decreased and plasma levels of OC be monitored in patients receiving CVVHDF because of acute kidney injury.
authors.affiliation: Pharmacy Department, Pitie-Salpetriere Hospital, Assistance Publique des Hôpitaux de Paris, AP-HP, Paris, France. florian.lemaitre@psl.aphp.fr
authors.forename: Florian
authors.initials: F
authors.lastname: Lemaitre
authors.forename: Charles-Edouard
authors.initials: CE
authors.lastname: Luyt
authors.forename: François
authors.initials: F
authors.lastname: Roullet-Renoleau
authors.forename: Ania
authors.initials: A
authors.lastname: Nieszkowska
authors.forename: Noël
authors.initials: N
authors.lastname: Zahr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Corvol
authors.forename: Christine
authors.initials: C
authors.lastname: Fernandez
authors.forename: Marie
authors.initials: M
authors.lastname: Antignac
authors.forename: Robert
authors.initials: R
authors.lastname: Farinotti
authors.forename: Alain
authors.initials: A
authors.lastname: Combes
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000628:therapy; D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods*; D005260:Female; D017583:Hemodiafiltration / Q000379:methods*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification; D007251:Influenza, Human / Q000150:complications; D008297:Male; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D058873:Pandemics; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000628:therapy; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; C535162:oseltamivir carboxylate