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Antimicrobial Agents and Chemotherapy, June 2005, p. 2367-2371, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2367-2371.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Penetration of Linezolid into Soft Tissues of Healthy Volunteers after Single and Multiple Doses

Pejman Dehghanyar,1 Cornelia Bürger,2 Markus Zeitlinger,1 Florian Islinger,1 Florian Kovar,1 Markus Müller,1 Charlotte Kloft,2 and Christian Joukhadar1,3*

Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Vienna, Austria,1 Department of Clinical Pharmacy, Freie Universität Berlin, Berlin, Germany,2 Department of Internal Medicine I, Division of Infectious Disease and Chemotherapy, Medical University of Vienna, Vienna, Austria3

Received 3 September 2004/ Returned for modification 31 December 2004/ Accepted 23 February 2005

The present study tested the ability of linezolid to penetrate soft tissues in healthy volunteers. Ten healthy volunteers were subjected to linezolid drug intake at a dose of 600 mg twice a day for 3 to 5 days. The first dose was administered intravenously. All following doses were self-administered orally. The tissue penetration of linezolid was assessed by use of in vivo microdialysis. In the single-dose experiments the ratios of the area under the concentration-time curve from 0 to 8 h (AUC0-8) for tissue to the AUC0-8 for free plasma were 1.4 ± 0.3 (mean ± standard deviation) and 1.3 ± 0.4 for subcutaneous adipose and muscle tissue, respectively. After multiple doses, the corresponding mean ratios were 0.9 ± 0.2 and 1.0 ± 0.5, respectively. The ratios of the AUC from 0 to 24 h (AUC0-24) for free linezolid in tissues to the MIC were between 50 and 100 for target pathogens with MICs between 2 and 4 mg/liter. In conclusion, the present study showed that linezolid penetrates rapidly into the interstitial space fluid of subcutaneous adipose and skeletal muscle tissues in healthy volunteers. On the basis of pharmacokinetic-pharmacodynamic calculations, we suggest that linezolid concentrations in soft tissues can be considered sufficient to inhibit the growth of many clinically relevant bacteria.

* Corresponding author. Mailing address: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Phone: 43-1-40400/2981. Fax: 43-1-40400/2998. E-mail: christian.joukhadar{at}meduniwien.ac.at.

Antimicrobial Agents and Chemotherapy, June 2005, p. 2367-2371, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2367-2371.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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