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rdf:type |
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lifeskim:mentions |
umls-concept:C0002679,
umls-concept:C0010592,
umls-concept:C0032105,
umls-concept:C0064113,
umls-concept:C0086045,
umls-concept:C0302350,
umls-concept:C0871261,
umls-concept:C1517004,
umls-concept:C1704632,
umls-concept:C1704675,
umls-concept:C1706817,
umls-concept:C1707455,
umls-concept:C1707520,
umls-concept:C2350529,
umls-concept:C2911692
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pubmed:issue |
6
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pubmed:dateCreated |
1994-10-17
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pubmed:abstractText |
Itraconazole and amphotericin B were compared by using a newly developed model of invasive pulmonary aspergillosis in rabbits immunosuppressed with methylprednisolone and cyclosporin A (CsA). Both itraconazole at 40 mg/kg (given orally) and amphotericin B at 1 mg/kg (given intravenously) had in vivo antifungal activity in comparison with controls. At these dosages, amphotericin B was more effective than itraconazole in reducing the tissue burden (log10 CFU per gram) of Aspergillus fumigatus (P < 0.05) and the number of pulmonary lesions (P < 0.01). However, there was considerable variation in the near-peak concentrations of itraconazole in plasma (median, 4.15 micrograms/ml; range, < 0.5 to 16.8 micrograms/ml) and a strong inverse correlation between concentrations of itraconazole in plasma and the tissue burden of A. fumigatus. An inhibitory sigmoid maximum-effect model predicted a significant pharmacodynamic relationship (r = 0.87, P < 0.001) between itraconazole concentrations in plasma and antifungal activity as a function of the tissue burden of A. fumigatus. This model demonstrated that levels in plasma of greater than 6 micrograms/ml were associated with a significantly greater antifungal effect. Levels in plasma of less than 6 micrograms/ml were associated with a rapid decline in the antifungal effect. Itraconazole, in comparison with amphotericin B, caused a twofold elevation of CsA levels (P < 0.01) but was less nephrotoxic (P < 0.01). This study of experimental pulmonary aspergillosis demonstrated that amphotericin B at 1 mg/kg/day was more active but more nephrotoxic than itraconazole at 40 mg/kg/day, that itraconazole increased concentrations of CsA in plasma, and that the antifungal activity of itraconazole strongly correlated with concentrations in plasma in an inhibitory sigmoid maximum-effect model. These findings further indicate the importance of monitoring concentrations of itraconazole in plasma as a guide to increasing dosage, improving bioavailability, and optimizing antifungal efficacy in the treatment of invasive pulmonary aspergillosis.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-1186493,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-1310577,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-1315160,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-1317280,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-1326309,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-1357148,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-1605615,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-1994248,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2066421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2159257,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2165371,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2170478,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2170481,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2247706,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2267490,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2540949,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2543220,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2552949,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2561187,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2886752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2889119,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2890938,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-2992106,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-3027843,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-3027853,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-3184859,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-3681380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-6340275,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-6660859,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8092829-872495
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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 |
Jun
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pubmed:issn |
0066-4804
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
38
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1303-8
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8092829-Amphotericin B,
pubmed-meshheading:8092829-Animals,
pubmed-meshheading:8092829-Aspergillosis,
pubmed-meshheading:8092829-Cyclosporine,
pubmed-meshheading:8092829-Drug Interactions,
pubmed-meshheading:8092829-Female,
pubmed-meshheading:8092829-Itraconazole,
pubmed-meshheading:8092829-Kidney,
pubmed-meshheading:8092829-Lung Diseases, Fungal,
pubmed-meshheading:8092829-Rabbits
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pubmed:year |
1994
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pubmed:articleTitle |
Itraconazole for experimental pulmonary aspergillosis: comparison with amphotericin B, interaction with cyclosporin A, and correlation between therapeutic response and itraconazole concentrations in plasma.
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pubmed:affiliation |
Infectious Diseases Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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