Pharmacokinetics of ertapenem in critically ill patients with acute renal failure undergoing extended daily dialysis

Abstract

Background. Extended (daily) dialysis (EDD) is an increasingly popular mode of renal replacement therapy in the ICU (intensive care unit) as it combines the advantages of intermittent haemodialysis (IHD) and continuous renal replacement therapy (CRRT), i.e. excellent detoxification accompanied by cardiovascular tolerability. The aim of this study was to evaluate pharmacokinetics (PK) of ertapenem, the newest carbapenem with once-daily dosing, in critically ill patients with anuric acute renal failure (ARF) undergoing EDD. Patients and Methods. In a single-centre, prospective, open-label study six ICU patients with ARF undergoing EDD were treated with 1 g ertapenem given as a single intravenous dose. EDD was performed using a high-flux dialyzer (polysulphone, 1.3 m2). Blood and dialysate flow were 160 mL/min, and the length of treatment was 480 min. Plasma samples were collected at different time-points up to 24 h after medication. Drug concentrations were determined by a validated LC-MS method. Free drug concentrations were estimated using a two-class binding site equation. Results. After a single dose of 1000 mg free ertapenem, protein-unbound plasma concentrations exceeded a MIC90 value of 2 mg/L for >20 h after dosing. The clearance of the tested dialyzer was 38.5 ± 14.2 mL/min. Conclusions. In contrast to patients undergoing regular IHD, in which a dose reduction is required, our data suggest that in patients treated with EDD a standard dose of ertapenem (1 g/day), i.e. dose for patients without renal failure, is required to maintain adequate plasma drug levels. © The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.