tetano
Editor, Senior Moderator
Ther Drug Monit. 2012 Feb 17. [Epub ahead of print]
Impact of Extracorporeal Membrane Oxygenation and Continuous Venovenous Hemodiafiltration on the Pharmacokinetics of Oseltamivir Carboxylate in Critically Ill Patients With Pandemic (H1N1) Influenza.
Lemaitre F, Luyt CE, Roullet-Renoleau F, Nieszkowska A, Zahr N, Corvol E, Fernandez C, Antignac M, Farinotti R, Combes A.
Source
From the *Pharmacy Department, Pitie-Salpetriere Hospital, Assistance Publique des H?pitaux de Paris, AP-HP, Paris; ?Clinical Pharmacy Unit, Paris Sud University, Chatenay-Malabry; ?Intensive Care Department, Pitie-Salpetriere Hospital, Assistance Publique des H?pitaux de Paris, AP-HP, Paris; ?Universite Paris 6, Pierre-et-Marie-Curie, Paris; and ?Pharmacology Department; and ‖Cardiac Surgery Department, Pitie-Salpetriere Hospital, Assistance Publique des H?pitaux de Paris, AP-HP, Paris, France.
Abstract
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.
PMID:
22354159
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22354159
Impact of Extracorporeal Membrane Oxygenation and Continuous Venovenous Hemodiafiltration on the Pharmacokinetics of Oseltamivir Carboxylate in Critically Ill Patients With Pandemic (H1N1) Influenza.
Lemaitre F, Luyt CE, Roullet-Renoleau F, Nieszkowska A, Zahr N, Corvol E, Fernandez C, Antignac M, Farinotti R, Combes A.
Source
From the *Pharmacy Department, Pitie-Salpetriere Hospital, Assistance Publique des H?pitaux de Paris, AP-HP, Paris; ?Clinical Pharmacy Unit, Paris Sud University, Chatenay-Malabry; ?Intensive Care Department, Pitie-Salpetriere Hospital, Assistance Publique des H?pitaux de Paris, AP-HP, Paris; ?Universite Paris 6, Pierre-et-Marie-Curie, Paris; and ?Pharmacology Department; and ‖Cardiac Surgery Department, Pitie-Salpetriere Hospital, Assistance Publique des H?pitaux de Paris, AP-HP, Paris, France.
Abstract
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.
PMID:
22354159
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22354159