Comparative assessment of tedizolid pharmacokinetics and tissue penetration between diabetic patients with wound infections and healthy volunteers via in vivo microdialysis

Sean M. Stainton, Marguerite L. Monogue, Arlinda Baummer-Carr, Ashley K. Shepard, James F. Nugent, Joseph L. Kuti, David P. Nicolau

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Herein, we present pharmacokinetic and tissue penetration data for oral tedizolid in hospitalized patients with diabetic foot infections (DFI) compared with healthy volunteers. Participants received oral tedizolid phosphate 200 mg every 24 h for 3 doses to achieve steady state. A microdialysis catheter was inserted into the subcutaneous tissue near the margin of the wound for patients or into thigh tissue of volunteers. Following the third dose, 12 blood and 14 dialysate fluid samples were collected over 24 h to characterize tedizolid concentrations in plasma and interstitial extracellular fluid of soft tissue. Mean ± standard deviation (SD) tedizolid pharmacokinetic parameters in plasma for patients compared with volunteers, respectively, were as follows: maximum concentration (Cmax), 1.5 ± 0.5 versus 2.7 ± 1.1 mg/liter (P = 0.005); time to Cmax (Tmax) (median [range]), 5.9 (1.2 to 8.0) versus 2.5 (2.0 to 3.0 h) (P = 0.003); half-life (t1/2), 9.1 ± 3.6 versus 8.9 ± 2.2 h (P = 0.932); and plasma area under the concentration-time curve for the dosing interval (AUCp), 18.5 ± 9.7 versus 28.7 ± 9.6 mg Å. h/liter (P = 0.004). The tissue area under the concentration-time curve (AUCt) for the dosing interval was 3.4 ± 1.5 versus 5.2 ± 1.6 mg Å. h/liter (P = 0.075). Tissue penetration median (range) was 1.1 (0.3 to 1.6) versus 0.8 (0.7 to 1.0) (P = 0.351). Despite lower plasma Cmax and delayed Tmax values for patients with DFI relative to healthy volunteers, the penetration into and exposure to tissue were similar. Based on available pharmacodynamic thresholds for tedizolid, the plasma and tissue exposures using the oral 200 mg once-daily regimen are suitable for further study in treatment of DFI.

Original languageEnglish (US)
Article numbere01880
JournalAntimicrobial agents and chemotherapy
Volume62
Issue number1
DOIs
StatePublished - Jan 2018
Externally publishedYes

Keywords

  • Diabetes
  • Microdialysis
  • Pharmacokinetics
  • Tedizolid
  • Tissue penetration

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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