Comparative Assessment of Tedizolid Pharmacokinetics and Tissue Penetration between Diabetic Patients with Wound Infections and Healthy Volunteers via In Vivo Microdialysis
| العنوان: | Comparative Assessment of Tedizolid Pharmacokinetics and Tissue Penetration between Diabetic Patients with Wound Infections and Healthy Volunteers via In Vivo Microdialysis |
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| المؤلفون: | Ashley Shepard, James Nugent, Marguerite L. Monogue, Arlinda Baummer-Carr, David P. Nicolau, Joseph L. Kuti, Sean M. Stainton |
| المصدر: | Antimicrobial Agents and Chemotherapy. 62 |
| بيانات النشر: | American Society for Microbiology, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, medicine.medical_specialty, Microdialysis, 030106 microbiology, Cmax, Urology, Administration, Oral, Biological Availability, Tetrazoles, Pharmacology, Diabetes Complications, 03 medical and health sciences, chemistry.chemical_compound, Pharmacokinetics, Extracellular fluid, Diabetes Mellitus, Humans, Medicine, Pharmacology (medical), Oxazolidinones, business.industry, Extracellular Fluid, Liter, Middle Aged, Healthy Volunteers, Anti-Bacterial Agents, Infectious Diseases, medicine.anatomical_structure, chemistry, Area Under Curve, Case-Control Studies, Pharmacodynamics, Wound Infection, Female, Tedizolid, business, Subcutaneous tissue |
| الوصف: | 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 ( C max ), 1.5 ± 0.5 versus 2.7 ± 1.1 mg/liter ( P = 0.005); time to C max ( T max ) (median [range]), 5.9 (1.2 to 8.0) versus 2.5 (2.0 to 3.0 h) ( P = 0.003); half-life (t 1/2 ), 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 (AUC p ), 18.5 ± 9.7 versus 28.7 ± 9.6 mg · h/liter ( P = 0.004). The tissue area under the concentration-time curve (AUC t ) for the dosing interval was 3.4 ± 1.5 versus 5.2 ± 1.6 mg · 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 C max and delayed T max 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. |
| تدمد: | 1098-6596 0066-4804 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::842d1b8cf1f59e18d860beb3bcd5ff68Test https://doi.org/10.1128/aac.01880-17Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....842d1b8cf1f59e18d860beb3bcd5ff68 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10986596 00664804 |
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