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Pharmacokinetic and pharmacodynamic evaluation of AZD5847 in a mouse model of tuberculosis.

ABSTRACT: AZD5847, a novel oxazolidinone with an MIC of 1 ?g/ml, exhibits exposure-dependent killing kinetics against extracellular and intracellular Mycobacterium tuberculosis. Oral administration of AZD5847 to mice infected with M. tuberculosis H37Rv in a chronic-infection model resulted in a 1.0-log10 reduction in the lung CFU count after 4 weeks of treatment at a daily area under the concentration-time curve (AUC) of 105 to 158 ?g · h/ml. The pharmacokinetic-pharmacodynamic parameter that best predicted success in an acute-infection model was an AUC for the free, unbound fraction of the drug/MIC ratio of ? 20. The percentage of time above the MIC in all of the efficacious regimens was 25% or greater.

SUBMITTER: Balasubramanian V

PROVIDER: S-EPMC4068583 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Pharmacokinetic and pharmacodynamic evaluation of AZD5847 in a mouse model of tuberculosis.

Balasubramanian V V Solapure Suresh S Shandil Radha R Gaonkar Sheshagiri S Mahesh K N KN Reddy Jitender J Deshpande Abhijeet A Bharath Sowmya S Kumar Naveen N Wright Lindsay L Melnick David D Butler Scott L SL

Antimicrobial agents and chemotherapy 20140512 7

AZD5847, a novel oxazolidinone with an MIC of 1 μg/ml, exhibits exposure-dependent killing kinetics against extracellular and intracellular Mycobacterium tuberculosis. Oral administration of AZD5847 to mice infected with M. tuberculosis H37Rv in a chronic-infection model resulted in a 1.0-log10 reduction in the lung CFU count after 4 weeks of treatment at a daily area under the concentration-time curve (AUC) of 105 to 158 μg · h/ml. The pharmacokinetic-pharmacodynamic parameter that best predict ...[more]

PMID: 24820085

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