title: Pharmacokinetics and penetration of moxifloxacin into infected diabetic foot tissue in a large diabetic patient cohort.
abstract: OBJECTIVE
  Physiological changes occurring in patients with diabetes may affect the pharmacokinetics and penetration of antimicrobial agents into peripheral tissue. We examined the pharmacokinetics and the penetration of moxifloxacin into perinecrotic tissue of diabetic foot lesions in patients with diabetic foot infections (DFI).
  
  
  METHODS
  Adult patients suffering from type 2 diabetes mellitus and hospitalized for DFI (Texas classification of at least B2) were treated with 400 mg moxifloxacin intravenously (IV) or orally (PO) once daily. The pharmacokinetics of moxifloxacin and its concentration 3 h after administration in samples of perinecrotic tissue resected from infected diabetic foot wounds were determined at steady state (days 4-8).
  
  
  RESULTS
  A total of 53 patients with diabetes mellitus type 2 (mean age 69.4 ± 10.8 years) were included in the study, of whom 28 received PO and 25 IV moxifloxacin therapy for a median of 8 days. In the PO and IV subgroups, the mean maximum observed plasma concentration (C (max)) in plasma was 2.69 and 4.77 mg/l at a median of 2 [time to reach C (max) (T (max)) range 1.0-8.0 h] and 1 h after administration, respectively. A mean area under the plasma concentration-time curve from time 0 until the last quantifiable plasma concentration (AUC(0-24 h)) of 29.36 mg h/l (PO) and 27.09 mg h/l (IV) was achieved. Mean moxifloxacin concentrations in perinecrotic tissue of infected diabetic foot wounds following PO or IV administration were 1.79 ± 0.82 and 2.20 ± 1.54 μg/g, thus exceeding the MIC(90) (minimum inhibitory concentration required to inhibit growth of 90% of organisms) for Staphylococcus aureus (0.25 mg/l) by seven- and eightfold and the MIC(90) for Escherichia coli (0.06 mg/l) by 29-fold and 36-fold, respectively. The mean tissue-to-plasma ratios of moxifloxacin concentration 3 h after administration were 1.01 ± 0.57 (PO) and 1.09 ± 0.69 (IV). Significant differences between the routes of administration were observed for T (max) and C (max) (P < 0.01), but not for other clinically relevant parameters (AUC(0-24); moxifloxacin DFI tissue concentration).
  
  
  CONCLUSIONS
  The plasma concentration-time curve of moxifloxacin in diabetic patients is similar to that of healthy volunteers. We also observed a good penetration of moxifloxacin into inflamed DFI tissue which taken together with the possibility of sequential IV/PO therapy suggest that moxifloxacin 400 mg once daily is a therapeutic option in the treatment of DFI caused by susceptible organisms.
authors.affiliation: Institute of Clinical Pharmacology, Centre of Pharmacology and Toxicology, University of Rostock, Schillingallee 70, 18057 Rostock, Germany. jolanta.majcher-peszynska@uni-rostock.de
authors.forename: Jolanta
authors.initials: J
authors.lastname: Majcher-Peszynska
authors.forename: Marko
authors.initials: M
authors.lastname: Sass
authors.forename: Sora
authors.initials: S
authors.lastname: Schipper
authors.forename: Viktor
authors.initials: V
authors.lastname: Czaika
authors.forename: Andreas
authors.initials: A
authors.lastname: Gussmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Lobmann
authors.forename: Ralf G
authors.initials: RG
authors.lastname: Mundkowski
authors.forename: Christoph
authors.initials: C
authors.lastname: Luebbert
authors.forename: Peter
authors.initials: P
authors.lastname: Kujath
authors.forename: Bernhard R
authors.initials: BR
authors.lastname: Ruf
authors.forename: Horst
authors.initials: H
authors.lastname: Koch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schareck
authors.forename: Ernst
authors.initials: E
authors.lastname: Klar
authors.forename: Bernd
authors.initials: B
authors.lastname: Drewelow
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001372:Aza Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy / Q000378:metabolism; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D017719:Diabetic Foot / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011446:Prospective Studies; D011804:Quinolines / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin