title: Penetration of linezolid into soft tissues of healthy volunteers after single and multiple doses.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Pejman
authors.initials: P
authors.lastname: Dehghanyar
authors.forename: Cornelia
authors.initials: C
authors.lastname: Bürger
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.forename: Florian
authors.initials: F
authors.lastname: Islinger
authors.forename: Florian
authors.initials: F
authors.lastname: Kovar
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kloft
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000273:Adipose Tissue / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D045604:Extracellular Fluid / Q000378:metabolism*; D006801:Humans; D000069349:Linezolid; D017551:Microdialysis / Q000379:methods; D018482:Muscle, Skeletal / Q000378:metabolism*; D023303:Oxazolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid