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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2003-6-24
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pubmed:abstractText |
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.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12821456-10223934,
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0066-4804
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pubmed:author |
pubmed-author:BalasubramanianVV,
pubmed-author:BharatSowmyaS,
pubmed-author:GaonkarSheshagiriS,
pubmed-author:JayaramRameshR,
pubmed-author:JayashreeRR,
pubmed-author:KantharajEE,
pubmed-author:KaurParvinderP,
pubmed-author:MaheshB NBN,
pubmed-author:NandiVrindaV,
pubmed-author:ShandilR KRK,
pubmed-author:SureshB LBL
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pubmed:issnType |
Print
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pubmed:volume |
47
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2118-24
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:12821456-Aerosols,
pubmed-meshheading:12821456-Animals,
pubmed-meshheading:12821456-Antibiotics, Antitubercular,
pubmed-meshheading:12821456-Cell Line,
pubmed-meshheading:12821456-Disease Models, Animal,
pubmed-meshheading:12821456-Dose-Response Relationship, Drug,
pubmed-meshheading:12821456-Female,
pubmed-meshheading:12821456-Macrophages,
pubmed-meshheading:12821456-Male,
pubmed-meshheading:12821456-Mice,
pubmed-meshheading:12821456-Mice, Inbred BALB C,
pubmed-meshheading:12821456-Microbial Sensitivity Tests,
pubmed-meshheading:12821456-Mycobacterium tuberculosis,
pubmed-meshheading:12821456-Rifampin,
pubmed-meshheading:12821456-Tuberculosis, Pulmonary
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pubmed:year |
2003
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pubmed:articleTitle |
Pharmacokinetics-pharmacodynamics of rifampin in an aerosol infection model of tuberculosis.
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pubmed:affiliation |
AstraZeneca India Pvt Ltd, Malleswaram, Bangalore 560003, India.
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pubmed:publicationType |
Journal Article,
In Vitro
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