Population Pharmacokinetics, Exposure-Efficacy, and Target Attainment Analyses of Tedizolid in Japanese and Chinese Subjects

Conference: ECCMID
Software: KIWI™
Division: Cognigen


  • Methicillin-resistant Staphylococcus aureus (MRSA) remains a threat for healthcare systems globally.1 MRSA frequently causes healthcare-associated infections and is associated with increased morbidity, mortality rate and length of hospital stay.1
  • There are a number of antibiotics with high in vitro potency, which are approved for the treatment of MRSA infections, although many of these antibiotics have limitations due to increased risk of toxicity or dosing challenges in special populations.2,3
  • In 2014, tedizolid phosphate, a novel oxazolidinone antibiotic, was approved by the US FDA for the treatment of acute bacterial skin and skin structure infections (ABSSSI) at the dose of 200 mg, once daily (QD) for 6 days.4 Tedizolid phosphate has recently been investigated versus linezolid in two randomised Phase 3 clinical studies for
    • 1) the treatment of skin and soft tissue infections (SSTI) in Japanese patients 5 and
    • 2) the treatment of ABSSSI in Chinese patients.6
  • Tedizolid phosphate is available in both intravenous (IV) and oral (PO) formulations at identical dosage (200 mg QD) and has a high oral bioavailability (i.e. Caucasian: 91.7 %, Japanese: 82.6 %, Chinese: 85.5 %, Korean: 95.2 % subjects).7 – 10
  • Analyses of previous Phase 1 studies indicated that no dose adjustment is required for the treatment of patients with moderate-to-severe renal impairment or severe hepatic impairment, for obese or morbidly obese patients, or for elderly patients.11 – 13
  • Population pharmacokinetic (popPK) analyses of pooled data from healthy subjects (who received single- or multiple-dose IV/PO tedizolid phosphate) and patients with ABSSSI who were treated with IV/PO tedizolid phosphate 200 mg QD supported that dose adjustments are not necessary based on patient age, sex, race, body weight, body mass index (BMI), renal function, or hepatic function.14
  • Previous population PK/PD analyses did not reveal any relationship between tedizolid exposures and efficacy (likely due to the attainment of a plateau in the exposure-response relationship with the limited exposure range from 200 mg dose administered in the Phase 3 trials), and suggested a minimum inhibitory concentration (MIC) of 0.5 μg/mL as the susceptibility breakpoint for S. aureus infections,14 which is approved by the US FDA, CLSI and EUCAST

European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Madrid, Spain, April 21-24, 2018

By Takahiko Tanigawa, Stefan Willmann, David Jaworowicz, Jill Fiedler-Kelly, Lily Li, Julie Passarell, Yoko Tanimura, Toshiaki Tanaka