Pharmacokinetic and Pharmacodynamic Evaluation of AZD5847 in a Mouse Model of Tuberculosis

被引：14

作者：

Balasubramanian, V. ^{[1
]}

Solapure, Suresh ^{[1
]}

Shandil, Radha ^{[1
]}

Gaonkar, Sheshagiri ^{[1
]}

Mahesh, K. N. ^{[1
]}

Reddy, Jitender ^{[1
]}

Deshpande, Abhijeet ^{[1
]}

Bharath, Sowmya ^{[1
]}

Kumar, Naveen ^{[1
]}

Wright, Lindsay ^{[2
]}

Melnick, David ^{[3
]}

Butler, Scott L. ^{[4
]}

机构：

[1] AstraZeneca India Pvt Ltd, Bangalore, Karnataka, India

[2] AstraZeneca UK, Macclesfield, Cheshire, England

[3] AstraZeneca, Wilmington, DC USA

[4] AstraZeneca R&D Boston, Waltham, MA USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2014年 / 58卷 / 07期

关键词：

DRUG-RESISTANT TUBERCULOSIS; IN-VIVO EFFICACY; MYCOBACTERIUM-TUBERCULOSIS; BACTERICIDAL ACTIVITY; MURINE MODEL; VITRO; OXAZOLIDINONE;

D O I：

10.1128/AAC.00137-14

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

AZD5847, a novel oxazolidinone with an MIC of 1 mu 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-log(10) 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 mu 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.

引用

页码：4185 / 4190

页数：6

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