Isoniazid Pharmacokinetics-Pharmacodynamics in an Aerosol Infection Model of Tuberculosis
| Autor: | E. Kantharaj, Ramesh Jayaram, B. L. Suresh, V. Balasubramanian, Radha Shandil, Vrinda Nandi, B. N. Mahesh, R. Jayashree, Sheshagiri Gaonkar, Parvinder Kaur, Sowmya Bharath |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Tuberculosis medicine.drug_class Antitubercular Agents Microbial Sensitivity Tests In Vitro Techniques Pharmacology Antimycobacterial Cell Line Mice Pharmacokinetics Isoniazid Animals Humans Medicine Experimental Therapeutics Pharmacology (medical) Chromatography High Pressure Liquid Antibacterial agent Aerosols Mice Inbred BALB C Dose-Response Relationship Drug business.industry Macrophages Dose fractionation Blood Proteins Mycobacterium tuberculosis medicine.disease Dose–response relationship Infectious Diseases Area Under Curve Pharmacodynamics Immunology Female business Protein Binding medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 48:2951-2957 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.48.8.2951-2957.2004 |
| Popis: | Limited 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 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/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 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). |
| Databáze: | OpenAIRE |
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