Pharmacokinetics of Tedizolid in Adults with Cystic Fibrosis

• Published in: Open forum infectious diseases 2017-10, Vol.4 (suppl_1), p.S293-S293
• Main Authors: Wang, Joshua, Park, Jenny, Jayne, Jordanna, Bensman, Timothy, D’Argenio, David, Fukushima, Lynn, Rao, Adupa, Beringer, Paul
• Format: Article
• Language: English
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofx163.670

Abstract Background The presence of MRSA in the airways of patients with CF is associated with more rapid lung function decline and a higher mortality. Tedizolid (TDZ) is an oxazolidinone antibiotic with potent activity against MRSA; however, the pharmacokinetics (PK) in CF have not been described. The purpose of this study was to determine the PK of IV/PO tedizolid in plasma in patients being treated for acute pulmonary exacerbations. Methods We conducted a prospective, multiple dose, randomized, crossover study. TDZ phosphate was administered as 200 mg IV over 1h or PO once daily x 3 under fed conditions, with a 2-day washout, followed by crossover. Laboratory studies were performed throughout the study as routine clinical care. Blood samples were obtained prior to the Third dose of IV and PO and at 8 additional timepoints over 48 hours. TDZ concentrations in plasma were determined by LC-MS/MS. The maximum concentration (Cmax) and time to maximum (Tmax) were obtained from the measured data. Area-under-the concentration curve (AUC24) was determined using the linear trapezoidal rule. Compartmental PK was performed using ADAPT 5 software. Data are described by mean ± SD. Results The patients (4M, 2F) had a mean age of 27 years (22–32), BMI 22.0 ± 4.2 kg/m2, and predicted creatinine clearance of 128 ± 44 mL/minute. There was one report of diarrhea and hoarseness of voice that was unlikely related to the study drug. There were no clinically relevant laboratory changes. The Cmax, Tmax, and AUC24 following IV and PO administration were 2.87 ± 0.64 mg/L / 2.26 ± 0.70 mg/L, 1.32 ± 0.49 hours /2.06 ± 1.29 hours, and 27.1 ± 4.74 mg/L x hours / 25.8 ± 6.03 mg/L x hours respectively. The PK parameters for TDZ were described by a 1-compartment model: Elimination rate constant (Kel) = 0.088 ± 0.014 hour-1, Volume of distribution (V) = 96.4 ± 27.4 L, absorption rate constant (Ka) = 0.869 ± 0.978 hours−1, and bioavailability (F) = 1.00 ± 0.101. Conclusion The oral bioavailability of TDZ in patients with CF is complete and the pharmacokinetics are similar to that reported for healthy volunteers indicating no dose adjustments are needed in future studies evaluating the efficacy and safety in patients with CF. Disclosures All authors: No reported disclosures.