Population Pharmacokinetics of AZD-5847 in Adults with Pulmonary Tuberculosis [PublishAheadOfPrint]

AZD-5847 is a new oxazolidinone derivative under development for the treatment of tuberculosis. In this study we describe the population pharmacokinetics 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 doses (500 mg once daily, 1200 mg once daily, 500 mg twice daily and 800 mg twice daily). Patients were intensively sampled on day 1 and 14. AZD-5847 pharmacokinetics were best described with a two compartment system with tlag for absorption. AZD-5847 bioavailability was nonlinear and plateaued at 800 mg. We performed deterministic simulation to compare the PKPD of AZD-5847, linezolid and sutezolid. AZD 5847 PKPD in terms of both fAUC/MIC and fT>MIC was less favorable compared to linezolid and sutezolid. This could help explain the poor bactericidal activity for AZD-5847 in the recent phase II study.

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