Pharmacokinetics of linezolid in septic patients with and without extended dialysis.
OBJECTIVE
Linezolid is an option for the treatment of infections caused by multiresistant Gram-positive bacteria. The survival of critically ill patients with acute renal failure (ARF) can be improved by increasing the dose of renal replacement therapy. Extended (daily) dialysis (ED) is a new and important approach to renal replacement therapy in intensive care units. The aim of the study was to evaluate the pharmacokinetics of linezolid in septic patients without ED and on ED, respectively.


METHODS
We studied the pharmacokinetics of linezolid in adult intensive care patients with sepsis (n = 5) and anuric septic patients with ARF being treated with ED (n = 10). Linezolid 600 mg was administered intravenously twice daily. The pharmacokinetic parameters, their variability, and possible covariates were analyzed using NONMEM.


RESULTS
The pharmacokinetics of linezolid followed a two-compartment model with clearance (Cl) = 0.159 L h(-1) kg(-1) +/- 51% (population mean +/- interindividual variability), central volume of distribution (V(1)) = 0.273 L/kg +/- 21%, intercompartmental clearance (Q) = 0.369 L h(-1) kg(-1), and peripheral volume of distribution (V(2)) = 0.271 L/kg. The clearance in ED patients while on dialysis was increased by 3.5 L/h, and patients with liver transplantation/resection had their clearance reduced by 60%. Intra-individual variability was much smaller than inter-individual variability.


CONCLUSIONS
Our results suggest that linezolid pharmacokinetics in critically ill patients with ARF undergoing ED is not comparable to that in healthy subjects and patients without ARF. The best method of managing linezolid dosage in such a complex group of patients, whose physiology can vary daily, would be to use therapeutic drug monitoring.
Swoboda
Stefanie
S
Pharmacy Department, University Hospital of Heidelberg, Germany. stefanie.swoboda@med.uni-heidelberg.de
Ober
Michael C
MC
Lichtenstern
Christoph
C
Saleh
Soundos
S
Schwenger
Vedat
V
Sonntag
Hans-Günther
HG
Haefeli
Walter Emil
WE
Hempel
Georg
G
Hoppe-Tichy
Torsten
T
Weigand
Markus A
MA
D000081:Acetamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D058186:Acute Kidney Injury / Q000097:blood / Q000150:complications / Q000628:therapy*; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003422:Critical Care; D016903:Drug Monitoring; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007262:Infusions, Intravenous; D000069349:Linezolid; D016031:Liver Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D023303:Oxazolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006435:Renal Dialysis / Q000379:methods*; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid