3 years ago

Comparative Assessment of Tedizolid Pharmacokinetics and Tissue Penetration Between Diabetic Patients with Wound Infections and Healthy Volunteers via In Vivo Microdialysis.

Joseph L Kuti, Marguerite L Monogue, Arlinda Baummer-Carr, David P Nicolau, James F Nugent, Sean M Stainton, Ashley K Shepard
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 200mg every 24 hours 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 3(rd) dose, 12 blood and 14 dialysate fluid samples were collected over 24 hours to characterize tedizolid concentrations in plasma and interstitial extracellular fluid of soft tissue. Mean ± SD tedizolid pharmacokinetic parameters in plasma for patients compared with volunteers, respectively, were: maximum concentration (Cmax) = 1.5 ± 0.5 versus 2.7 ± 1.1 mg/L (p=0.005), time to Cmax (Tmax) [median (range)] = 5.9 (1.2-8.0) versus 2.5 (2.0-3.0 hours (p=0.003), half-life (t1/2) = 9.1 ± 3.6 versus 8.9 ± 2.2 hours (p=0.932), and plasma area under the curve for the dosing interval (AUCp) = 18.5 ± 9.7 versus 28.7 ± 9.6 mg·h/L (p=0.004). The tissue AUC for the dosing interval was 3.4 ± 1.5 versus 5.2 ± 1.6 mg·h/L (p=0.075). Tissue penetration, median (range) was 1.1 (0.3 - 1.6) versus 0.8 (0.7-1.0) (p=0.351). Despite lower plasma Cmax and delayed Tmax values for patients with DFI relative to healthy volunteers, the penetration and exposure into tissue were similar. Based on available pharmacodynamic thresholds for tedizolid, the plasma and tissue exposures using the oral 200mg once-daily regimen are suitable for further study in treatment of DFI.

Publisher URL: http://doi.org/10.1128/AAC.01880-17

DOI: 10.1128/AAC.01880-17

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