Tedizolid Population Pharmacokinetics, Exposure-Response, and Target Attainment

Conference: ICAAC
Division: Cognigen


  •  Tedizolid phosphate is a novel antibiotic prodrug rapidly converted by phosphatases to its active moiety tedizolid after administration1. Tedizolid is 4-16 fold more potent in vitro than linezolid against Gram-positive pathogens, incl. methicillin-resistant Staphylococcus aureus and strains resistant to linezolid or vancomycin2-4 and is rapidly bactericidal in vivo5. Tedizolid phosphate is administered once daily (orally or IV at identical dosage).
    In clinical studies, tedizolid has demonstrated a favorable pharmacokinetic (PK) profile in healthy volunteers, including a long half-life, minimal accumulation over time, high oral bioavailability (> 80%), and low inter-patient variability in drug exposure levels1.
  • Once daily dosing regimens of 200, 300, or 400 mg resulted in similar efficacy outcomes in a Phase 2 study6.
  • In two recent Phase 3 trials, a 6-day course of tedizolid phosphate 200 mg once/day demonstrated non-inferior efficacy to a 10-day course of linezolid 600 mg twice/day for the treatment of acute bacterial skin and soft tissue infections (ABSSSI), with improved gastrointestinal tolerability and a reduced potential for hematological toxicity7,8.
  • A population pharmacokinetic model was developed to evaluate the impact of tedizolid exposures on efficacy and safety, factors influencing PK and PK/pharmacodynamic (PK/PD) variability, and the probability of attaining the tedizolid PK/PD target measure.

Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Denver, Colorado, September 2013

By S. Flanagan, Julie A. Passarell, Q. Lu, Jill Fiedler-Kelly, P. Prokocimer