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


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 m(2)). 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 MIC(90) 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.
Burkhardt
Olaf
O
Department of Pulmonary Medicine, Medical School Hannover, Hannover, Germany.
Hafer
Carsten
C
Langhoff
Anita
A
Kaever
Volkhard
V
Kumar
Vipul
V
Welte
Tobias
T
Haller
Hermann
H
Fliser
Danilo
D
Kielstein
Jan T
JT
D058186:Acute Kidney Injury / Q000097:blood* / Q000628:therapy*; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016638:Critical Illness; D004334:Drug Administration Schedule; D000077727:Ertapenem; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods*; D047090:beta-Lactams / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077727:Ertapenem