Pharmacokinetics-Pharmacodynamics of Rifampin in an Aerosol Infection Model of Tuberculosis
| Autor: | E. Kantharaj, Parvinder Kaur, R. Jayashree, Ramesh Jayaram, B. L. Suresh, Radha Shandil, Sheshagiri Gaonkar, V. Balasubramanian, B. N. Mahesh, Sowmya Bharat, Vrinda Nandi |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.drug_class Antibiotics Microbial Sensitivity Tests In Vitro Techniques Biology Cell Line Microbiology Mycobacterium tuberculosis Mice Pharmacokinetics In vivo medicine Animals Potency Experimental Therapeutics Pharmacology (medical) Antibiotics Antitubercular Tuberculosis Pulmonary Aerosols Pharmacology Mice Inbred BALB C Dose-Response Relationship Drug Macrophages biology.organism_classification Disease Models Animal Dose–response relationship Infectious Diseases Pharmacodynamics Female Rifampin Rifampicin medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 47:2118-2124 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.47.7.2118-2124.2003 |
| Popis: | Limited information exists on the pharmacokinetic (PK)-pharmacodynamic (PD) relationships of drugs against Mycobacterium tuberculosis . Our aim was to identify the PK-PD parameter that best describes the efficacy of rifampin on the basis of in vitro and PK properties. Consistent with 83.8% protein binding by equilibrium dialysis, the rifampin MIC for M. tuberculosis strain H37Rv rose from 0.1 in a serum-free system to 1.0 mg/ml when it was tested in the presence of 50% serum. In time-kill studies, rifampin exhibited area under the concentration-time curve (AUC)-dependent killing in vitro, with maximal killing seen on all days and with the potency increasing steadily over a 9-day exposure period. MIC and time-kill studies performed with intracellular organisms in a macrophage monolayer model yielded similar results. By use of a murine aerosol infection model with dose ranging and dose fractionation over 6 days, the PD parameter that best correlated with a reduction in bacterial counts was found to be AUC/MIC ( r 2 = 0.95), whereas the maximum concentration in serum/MIC ( r 2 = 0.86) and the time that the concentration remained above the MIC ( r 2 = 0.44) showed lesser degrees of correlation. |
| Databáze: | OpenAIRE |
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