| Autor: |
Jayaram, Ramesh, Shandil, Radha. K., Gaonkar, Sheshagiri, Kaur, Parvinder, Suresh, B. L., Mahesh, B. N., Jayashree, R., Nandi, Vrinda, Bharath, Sowmya, Kantharaj, E., Balasubramanian, V. |
| Zdroj: |
Antimicrobial Agents and Chemotherapy; August 2004, Vol. 48 Issue: 8 p2951-2957, 7p |
| Abstrakt: |
ABSTRACTLimited data exist on the pharmacokinetic-pharmacodynamic (PK-PD) parameters of the bactericidal activities of the available antimycobacterial drugs. We report on the PK-PD relationships for isoniazid. Isoniazid exhibited concentration (C)-dependent killing of Mycobacterium tuberculosisH37Rv in vitro, with a maximum reduction of 4 log10CFU/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-log10CFU/ml 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 log10CFU/lung. Dose fractionation studies demonstrated that the 24-h area under the concentration-time curve/MIC (r2= 0.83) correlated best with the bactericidal efficacy, followed by the maximum concentration of drug in serum/MIC (r2= 0.73). |
| Databáze: |
Supplemental Index |
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