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JAC Advance Access originally published online on November 13, 2007
Journal of Antimicrobial Chemotherapy 2008 61(1):173-176; doi:10.1093/jac/dkm431
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Effect of severity of sepsis on tissue concentrations of linezolid

Christiane Thallinger1,2, Cornelia Buerger3, Nele Plock3, Sascha Kljucar4, Sonja Wuenscher1, Robert Sauermann1, Charlotte Kloft3 and Christian Joukhadar5,*

1 Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria 2 Department of Internal Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria 3 Department of Clinical Pharmacy, Institute of Pharmacy, Freie Universität Berlin/Martin-Luther-Universität Halle-Wittenberg, 12169 Berlin/06120 Halle, Germany 4 DRK Kliniken Berlin Westend, Berlin, Germany 5 Department of Internal Medicine II, Division of Pulmonology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria

Received 9 July 2007; returned 23 August 2007; revised 8 October 2007; accepted 10 October 2007

* Correspondence address. Schafflerhofstr. 149, 1220 Vienna, Austria. Tel: +43-664-462-86-25; E-mail: christian.joukhadar{at}gmx.at

Objectives: In the present study, we examined whether differences in the severity of sepsis translate to differences in the pharmacokinetic profile of linezolid in plasma and the interstitium of target tissues after a single intravenous dose of 600 mg by means of the microdialysis technique.

Patients and methods: A total of 24 patients were included in the trial. Sixteen patients suffered from septic shock and eight patients presented with severe sepsis. Sepsis was diagnosed and verified according to the criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. Historic data derived from a previous study determining the pharmacokinetic profiles of linezolid in tissues and plasma in young healthy volunteers served as controls.

Results: In the present study, the AUC for free linezolid from 0 to 24 h (fAUC0–24) ranged from 50 to 71 mg·h/L after single-dose administration in patients presenting with severe sepsis or septic shock. The mathematically extrapolated fAUC0–24 ranged from 100 to 146 mg·h/L for twice-daily administration and a dosing interval of 12 h. No statistically significant difference in key pharmacokinetic parameters was detected between patients suffering from severe sepsis and septic shock (P > 0.05).

Conclusions: These data indicated that the severity of sepsis has no substantial effect on the pharmacokinetic profile of linezolid in plasma and in the interstitium of soft tissues.

Keywords: pharmacokinetics , inflammation , single-dose


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