Isoniazid pharmacokinetics-pharmaco dynamics in an aerosol infection model of tuberculosis

被引：136

作者：

Jayaram, R ^{[1
]}

Shandil, RK ^{[1
]}

Gaonkar, S ^{[1
]}

Kaur, P ^{[1
]}

Suresh, BL ^{[1
]}

Mahesh, BN ^{[1
]}

Jayashree, R ^{[1
]}

Nandi, V ^{[1
]}

Bharath, S ^{[1
]}

Kantharaj, E ^{[1
]}

Balasubramanian, V ^{[1
]}

机构：

[1] AstraZeneca India Pvt Ltd, Bangalore 560024, Karnataka, India

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2004年 / 48卷 / 08期

关键词：

D O I：

10.1128/AAC.48.8.2951-2957.2004

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Limited data exist on the pharmacokinetic-pharmacodynamic (PK-PD) parameters of the bactericidal activities of the available anti mycobacterial drugs. We report on the PK-PD relationships for isoniazid. Isoniazid exhibited concentration (C)-dependent killing of Mycobacterium tuberculosis H37Rv in vitro, with a maximum reduction of 4 log(10) CFU/ml. In these studies, 50% of the maximum effect was achieved at a C/MIC ratio of 0.5, and the maximum effect did not increase with exposure times of up to 21 days. Conversely, isoniazid produced less than a 0.5-log(10) CFU/mI reduction in two different intracellular infection models (J774A.1 murine macrophages and whole human blood). In a murine model of aerosol infection, isoniazid therapy for 6 days produced a reduction of 1.4 log(10) CFU/lung. Dose fractionation studies demonstrated that the 24-h area under the concentration-time curve/MIC (r(2) = 0.83) correlated best with the bactericidal efficacy, followed by the maximum concentration of drug in serum/MIC (r(2) = 0.73).

引用

页码：2951 / 2957

页数：7

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