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Population Pharmacokinetics of AZD-5847 in Adults with Pulmonary Tuberculosis.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2017 Sep 22; Vol. 61 (10). Date of Electronic Publication: 2017 Sep 22 (Print Publication: 2017). - Publication Year :
- 2017
-
Abstract
- 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 ( T <subscript>lag</subscript> ) 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 ( f AUC)/MIC and time the free concentration was above the MIC ( f T>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.<br /> (Copyright © 2017 American Society for Microbiology.)
- Subjects :
- Adolescent
Adult
Aged
Antitubercular Agents therapeutic use
Biological Availability
Female
Humans
Linezolid pharmacokinetics
Male
Microbial Sensitivity Tests
Middle Aged
Oxazolidinones therapeutic use
Young Adult
Antitubercular Agents pharmacokinetics
Oxazolidinones pharmacokinetics
Tuberculosis, Pulmonary drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1098-6596
- Volume :
- 61
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 28739794
- Full Text :
- https://doi.org/10.1128/AAC.01066-17