Population Pharmacokinetics of AZD-5847 in Adults with Pulmonary Tuberculosis

Antimicrob Agents Chemother. 2017 Sep 22;61(10):e01066-17. doi: 10.1128/AAC.01066-17. Print 2017 Oct.


AZD-5847 is a new oxazolidinone derivative under development for the treatment of tuberculosis (TB). Here we describe the population pharmacokinetics (PK) of AZD-5847 in patients with tuberculosis based on a recently completed phase II study. The study included 60 patients with drug-susceptible TB. Patients were randomized to four dosages (500 mg once daily, 1,200 mg once daily, 500 mg twice daily, and 800 mg twice daily). Patients were intensively sampled on days 1 and 14. AZD-5847 pharmacokinetics were best described with a two-compartment model with lag time (Tlag) for absorption. AZD-5847 bioavailability was nonlinear and plateaued at 800 mg. We performed deterministic simulation to compare the PK/pharmacodynamics (PD) of AZD-5847, linezolid, and sutezolid. AZD-5847 PK/PD in terms of both area under the concentration-time curve for the free, unbound fraction (fAUC)/MIC and time the free concentration was above the MIC (fT>MIC) were less favorable than those for linezolid and sutezolid. This could help explain the poor bactericidal activity of AZD-5847 in the recent phase II study.

Keywords: AZD-5847; pharmacokinetics; tuberculosis.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antitubercular Agents / pharmacokinetics*
  • Antitubercular Agents / therapeutic use
  • Biological Availability
  • Female
  • Humans
  • Linezolid / pharmacokinetics
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Oxazolidinones / pharmacokinetics*
  • Oxazolidinones / therapeutic use
  • Tuberculosis, Pulmonary / drug therapy*
  • Young Adult


  • Antitubercular Agents
  • Oxazolidinones
  • PNU-100480
  • posizolid
  • Linezolid