tetano
Editor, Senior Moderator
Int J Antimicrob Agents
. 2026 Oct 29:108046.
doi: 10.1016/j.ijantimicag.2026.108046. Online ahead of print.
Mohd H Abdul-Aziz 1 , Vesa Cheng 2 , Fay Burrows 3 , Hergen Buscher 4 , Amanda Corley 5 , Eileen Gilder 6 , Xin Liu 2 , Shay Mcguinness 7 , Saurabh Pandey 2 , Rachael Parke 6 , Diane Maresco-Pennisi 2 , Claire Reynolds 8 , Sam Rudham 8 , Steven C Wallis 2 , Susan A Welch 3 , Jiao Xie 9 , John F Fraser 10 , Kiran Shekar 11 , Jason A Roberts 12
Affiliations Expand
Objectives: To characterise the population pharmacokinetics of oseltamivir and oseltamivir carboxylate in critically ill adults receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) without renal replacement therapy (RRT), and to compare oseltamivir carboxylate exposure with an exploratory exposure-response threshold and published pharmacokinetic data.
Methods: This multinational ASAP ECMO analysis included 8 critically ill adults receiving oseltamivir 75 mg every 12 hours during VV-ECMO. Serial blood samples were collected over a dosing interval, and oseltamivir and oseltamivir carboxylate concentrations were measured using a validated assay. Population pharmacokinetic modelling was performed in Monolix using an integrated parent drug-metabolite model.
Results: Fifty-eight plasma concentration-time points were available for analysis. The cohort was relatively young and 63% had augmented renal clearance (ARC). A one-compartment model best described both oseltamivir and oseltamivir carboxylate, with a transit compartment required to account for delayed metabolite formation. Median oseltamivir carboxylate exposure was generally comparable to values reported in healthy adults and critically ill patients receiving standard dosing. Median oseltamivir carboxylate area under the concentration-time curve from 0-12 hours (AUC0-12) was lower in patients with ARC than in those without (1877.78 vs. 8253.39 ng·h/mL; p=0.07). Only 2 of 8 patients achieved the primary exploratory exposure-response threshold (AUC0-12 ≥7000 ng∙h/mL) and none of the 5 patients with ARC achieved this threshold.
Conclusions: Marked variability and lower exposure were observed in adults receiving VV-ECMO without RRT, particularly ARC patients. Higher doses may be required in ARC patients, but the optimal dosing regimen remains undefined. Routine dose escalation is not supported by current evidence.
Keywords: augmented renal clearance; extracorporeal membrane oxygenation (ECMO); neuraminidase inhibitors; pharmacokinetics; severe influenza.
. 2026 Oct 29:108046.
doi: 10.1016/j.ijantimicag.2026.108046. Online ahead of print.
Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in critically ill adults receiving veno-venous extracorporeal membrane oxygenation without renal replacement therapy - an ASAP ECMO study
Mohd H Abdul-Aziz 1 , Vesa Cheng 2 , Fay Burrows 3 , Hergen Buscher 4 , Amanda Corley 5 , Eileen Gilder 6 , Xin Liu 2 , Shay Mcguinness 7 , Saurabh Pandey 2 , Rachael Parke 6 , Diane Maresco-Pennisi 2 , Claire Reynolds 8 , Sam Rudham 8 , Steven C Wallis 2 , Susan A Welch 3 , Jiao Xie 9 , John F Fraser 10 , Kiran Shekar 11 , Jason A Roberts 12
Affiliations Expand
- PMID: 42956910
- DOI: 10.1016/j.ijantimicag.2026.108046
Abstract
Objectives: To characterise the population pharmacokinetics of oseltamivir and oseltamivir carboxylate in critically ill adults receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) without renal replacement therapy (RRT), and to compare oseltamivir carboxylate exposure with an exploratory exposure-response threshold and published pharmacokinetic data.
Methods: This multinational ASAP ECMO analysis included 8 critically ill adults receiving oseltamivir 75 mg every 12 hours during VV-ECMO. Serial blood samples were collected over a dosing interval, and oseltamivir and oseltamivir carboxylate concentrations were measured using a validated assay. Population pharmacokinetic modelling was performed in Monolix using an integrated parent drug-metabolite model.
Results: Fifty-eight plasma concentration-time points were available for analysis. The cohort was relatively young and 63% had augmented renal clearance (ARC). A one-compartment model best described both oseltamivir and oseltamivir carboxylate, with a transit compartment required to account for delayed metabolite formation. Median oseltamivir carboxylate exposure was generally comparable to values reported in healthy adults and critically ill patients receiving standard dosing. Median oseltamivir carboxylate area under the concentration-time curve from 0-12 hours (AUC0-12) was lower in patients with ARC than in those without (1877.78 vs. 8253.39 ng·h/mL; p=0.07). Only 2 of 8 patients achieved the primary exploratory exposure-response threshold (AUC0-12 ≥7000 ng∙h/mL) and none of the 5 patients with ARC achieved this threshold.
Conclusions: Marked variability and lower exposure were observed in adults receiving VV-ECMO without RRT, particularly ARC patients. Higher doses may be required in ARC patients, but the optimal dosing regimen remains undefined. Routine dose escalation is not supported by current evidence.
Keywords: augmented renal clearance; extracorporeal membrane oxygenation (ECMO); neuraminidase inhibitors; pharmacokinetics; severe influenza.