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Impact of Extracorporeal Membrane Oxygenation and Continuous Venovenous Hemodiafiltration on the Pharmacokinetics of Oseltamivir Carboxylate in Critically Ill Patients With Pandemic (H1N1) Influenza

Lemaitre, Florian PharmD*,†; Luyt, Charles-Edouard MD‡,§; Roullet-Renoleau, François*; Nieszkowska, Ania MD‡,§; Zahr, Noël PharmD, PhD; Corvol, Emmanuel; Fernandez, Christine PharmD, PhD*,†; Antignac, Marie PharmD, PhD*; Farinotti, Robert PharmD, PhD*,†; Combes, Alain MD, PhD‡,§

doi: 10.1097/FTD.0b013e318248672c
Original Article

Purpose: 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.

Patients and 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.

*Pharmacy Department, Pitie-Salpetriere Hospital, Assistance Publique des Hôpitaux de Paris, AP-HP, Paris

Clinical Pharmacy Unit, Paris Sud University, Chatenay-Malabry

Intensive Care Department, Pitie-Salpetriere Hospital, Assistance Publique des Hôpitaux de Paris, AP-HP, Paris

§Universite Paris 6, Pierre-et-Marie-Curie, Paris

Pharmacology Department

Cardiac Surgery Department, Pitie-Salpetriere Hospital, Assistance Publique des Hôpitaux de Paris, AP-HP, Paris, France.

The authors declare no conflicts of interest.

Correspondence: Florian Lemaitre, PharmD, Pitie-Salpetriere Hospital, Assistance Publique des Hôpitaux de Paris, AP-HP, Paris, France (e-mail: florian.lemaitre@psl.aphp.fr).

Received July 26, 2011

Accepted December 27, 2011

© 2012 Lippincott Williams & Wilkins, Inc.