title: Target site pharmacokinetics of linezolid after single and multiple doses in diabetic patients with soft tissue infection.
abstract: The underlying pathology of diabetic wounds, i.e. impairment of macro- and microcirculation, might also impact target site penetration of antibacterial drugs. To compare tissue concentrations of linezolid in infected and not infected tissue 10 patients suffering from type 2 diabetes with foot infection were included in the study. Tissue penetration of linezolid was assessed using in vivo microdialysis at the site of infection as well as in non-inflamed subcutaneous adipose tissue. All patients were investigated after receiving a single dose of linezolid and five patients in addition at steady state. After a single dose of linezolid significantly higher area under the concentration vs. time curve over 8 hours (AUC0-8 ) and maximum concentrations (Cmax )-values were observed in plasma (65.5 ± 21.2 mg*h/L and 16.4 ± 4.6 mg/L) as compared to inflamed (36.3 ± 22.9  mg*h/L and 6.6 ± 3.6 mg/L) and non-inflamed tissue (33.0 ± 17.7 mg*h/L and 6.7 ± 3.6 mg/L). Multiple administrations of linezolid led to disappearance of significant differences in Cmax and AUC0-8 between plasma, inflamed, and non-inflamed tissue. Approximately 2-fold increase of Cmax and AUC0-8 -values in tissue was observed at steady state as compared to the first administration. Penetration of linezolid is not impaired in diabetic foot infection but equilibrium between plasma and tissue might be delayed.
authors.affiliation: Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Roza Badr
authors.initials: RB
authors.lastname: Eslam
authors.forename: Angela
authors.initials: A
authors.lastname: Burian
authors.forename: Greisa
authors.initials: G
authors.lastname: Vila
authors.forename: Robert
authors.initials: R
authors.lastname: Sauermann
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hammer
authors.forename: Dorothea
authors.initials: D
authors.lastname: Frenzel
authors.forename: Iris K
authors.initials: IK
authors.lastname: Minichmayr
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kloft
authors.forename: Peter
authors.initials: P
authors.lastname: Matzneller
authors.forename: Zoe
authors.initials: Z
authors.lastname: Oesterreicher
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005534:Foot Diseases / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D000069349:Linezolid; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018461:Soft Tissue Infections / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid
keywords: inflammation; linezolid; pharmacokinetics; tissue