2. Academic Validation
  3. Pharmacokinetic and pharmacodynamic evaluation of AZD5847 in a mouse model of tuberculosis

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

  • Antimicrob Agents Chemother. 2014 Jul;58(7):4185-90. doi: 10.1128/AAC.00137-14.
V Balasubramanian 1,  Suresh Solapure 2,  Radha Shandil 1,  Sheshagiri Gaonkar 1,  K N Mahesh 1,  Jitender Reddy 1,  Abhijeet Deshpande 1,  Sowmya Bharath 1,  Naveen Kumar 1,  Lindsay Wright 3,  David Melnick 4,  Scott L Butler 5
Affiliations

Affiliations

  • 1 AstraZeneca India Pvt. Ltd., Hebbal, Bangalore, India.
  • 2 AstraZeneca India Pvt. Ltd., Hebbal, Bangalore, India suresh.solapure@astrazeneca.com.
  • 3 AstraZeneca UK, Mereside, Alderly Park, Macclesfield, Cheshire, England.
  • 4 AstraZeneca Pharmaceuticals, Wilmington, Delaware, USA.
  • 5 AstraZeneca R&D Boston, Waltham, Massachusetts, USA.
PMID: 24820085 DOI: 10.1128/AAC.00137-14
Abstract

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 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.

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