| Autor: |
Maki, Katsuyuki, Watabe, Etsuko, Iguchi, Yumi, Nakamura, Hideko, Tomishima, Masaki, Ohki, Hidenori, Yamada, Akira, Matsumoto, Satoru, Ikeda, Fumiaki, Tawara, Shuichi, Mutoh, Seitaro |
| Zdroj: |
Microbiology and Immunology; April 2006, Vol. 50 Issue: 4 p281-292, 12p |
| Abstrakt: |
To establish an in vitromethod of predicting in vivoefficacy of antifungal drugs against Candida albicansand Aspergillus fumigatus, the antifungal activities of fluconazole, itraconazole, and amphotericin B were determined in mouse serum. The minimum inhibitory concentration (MIC) of each drug was measured using mouse serum as a diluent. For C. albicans, the assay endpoint of azoles was defined as inhibition of mycelial extension (mMIC) and for A. fumigatus, as no growth (MIC). The MICs of amphotericin B for both pathogens were defined as the MIC at which no mycelial growth occurred. Serum MIC or mMIC determinations were then used to estimate the concentration of the drugs in serum of mice treated with antifungal drugs by multiplying the antifungal titer of the serum samples by the serum (m)MIC. The serum drug concentrations were also determined by HPLC. The serum concentrations estimated microbiologically showed good agreement with those determined by HPLC, except for itraconazole. Analysis of the serum samples from itraconazole‐treated mice by a sensitive bioautography revealed the presence of additional spots, not seen in control samples of itraconazole. The bioautography assay demonstrated that the additional material detected in serum from mice treated with itraconazole was an active metabolite of itraconazole. The data showed that the apparent reduction in the itraconazole serum concentration as determined by HPLC was the result of the formation of an active metabolite, and that the use of a microbiological method to measure serum concentrations of drugs can provide a method for prediction of in vivoefficacy of antifungal drugs. |
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