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

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 (), 1.5 ± 0.5 versus 2.7 ± 1.1 mg/liter ( = 0.005); time to () (median [range]), 5.9 (1.2 to 8.0) versus 2.5 (2.0 to 3.0 h) ( = 0.003); half-life (t), 9.1 ± 3.6 versus 8.9 ± 2.2 h ( = 0.932); and plasma area under the concentration-time curve for the dosing interval (AUC ), 18.5 ± 9.7 versus 28.7 ± 9.6 mg · h/liter ( = 0.004). The tissue area under the concentration-time curve (AUC ) for the dosing interval was 3.4 ± 1.5 versus 5.2 ± 1.6 mg · h/liter ( = 0.075). Tissue penetration median (range) was 1.1 (0.3 to 1.6) versus 0.8 (0.7 to 1.0) ( = 0.351). Despite lower plasma and delayed 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.

Pharmacokinetics of Tedizolid in an Obese Patient after Bariatric Surgery

“…AUC from 0 to 24 h (AUC 0 -24 ) was 28.3 mg/liter • h for total concentrations, and the terminal half-life (t 1/2 ) was 11 h. These results are presented in Table 1 together with values found in recently published papers for comparison. The pharmacokinetic parameters are close to those previously reported, suggesting that this particularly restrictive type of bariatric surgery has a limited impact, if any, on tedizolid pharmacokinetics (2,8,9). AUC 0 -24 for unbound concentrations (fAUC 0 -24 ) was 5.40 mg/liter • h, corresponding to an average unbound fraction of 19%, consistent with previously published values (10).…”

Pharmacokinetics and Pharmacodynamics of Tedizolid

“…Similarly, no disparity in PK profiles was noted in morbidly obese patients compared to the nonobese subjects [23]. There were no significant Table 1 Pharmacokinetic parameters of tedizolid at a therapeutic dosage (200 mg/day) AUC 0-∞ AUC from zero to infinity, AUC 0-24 AUC from 0 to 24 hours, C max maximum concentration, IV intravenous, SD standard deviation from the mean, V d volume of distribution a AUC = area under the concentration-time curve Data from [4,5,15,18,20,21,25,28]…”

“… AUC 0–∞ AUC from zero to infinity, AUC 0–24 AUC from 0 to 24 hours, C max maximum concentration, IV intravenous, SD standard deviation from the mean, V d volume of distribution a AUC = area under the concentration–time curve Data from [ 4 , 5 , 15 , 18 , 20 , 21 , 25 , 28 ] …”

Importance and Reality of TDM for Antibiotics Not Covered by Insurance in Japan

“…Several methods for the quantification of TZD in plasma using HPLC have been reported [ 69 , 70 , 71 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ]. In Japan, three reports were published in 2020–2021.…”