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Penetration of ravuconazole, a new triazole antifungal, into rat tissues
Hiroshiege Mikamo1, Xiang Hua Yin, Yoh Hayasaki
1Department of Obstetrics and Gynecology, School of Medicine, Gifu University, Japan. mikamo@cc.gifu-u.ac.jp
Abstract:
Ravuconazole (BMS 207147, ER-30346) is a long-lasting triazole antifungal agent active against a broad spectrum of fungal pathogens including non-albicans Candida, Aspergillus, Cryptococcus and key dermatophytic fungi. The penetration of ravuconazole into rat tissues was examined. Fifty-five 7-week-old specific pathogen free female rats were used in this study. Plasma, lung and uterus tissue of rats were taken at 1, 2, 4, 8, 12, 16, 24, 32, 48, 60, and 72 h (n = 5) after oral administration of 10 mg/kg of ravuconazole. The quantitative assays of ravuconazole by HPLC after the extraction with diethylether were conducted for each tissue sample homogenate. tmax, t1/2, and Cmax of ravuconazole is 8 h, 16.9 h and 1.68 microg/ml, respectively. The concentrations of ravuconazole in rat uterus and lung tissues were 2-to 6 times higher than the corresponding blood concentrations. The ratio of plasma to lung levels of ravuconazole was superior to the published data of other azoles. Considering its antifungal spectrum, ravuconazole would thus be a good candidate for treatment of deep-seated fungal infections caused by Candida, Aspergillus and Cryptococcus.
Insights
Ravuconazole, a potent triazole antifungal, demonstrates excellent penetration into rat lung and uterus tissues. This broad-spectrum agent shows promising potential for treating deep-seated fungal infections.
Area of Science:
- Pharmacology
- Mycology
- Drug Discovery
Background:
- Ravuconazole is a long-acting triazole antifungal with broad-spectrum activity against various fungal pathogens.
- Includes activity against non-albicans Candida, Aspergillus, Cryptococcus, and dermatophytes.
Purpose of the Study:
- To investigate the tissue penetration of ravuconazole in rats.
- To determine pharmacokinetic parameters and tissue distribution after oral administration.
Main Methods:
- Oral administration of 10 mg/kg ravuconazole to 55 female rats.
- Plasma, lung, and uterus samples collected at various time points (1-72 hours).
- Quantitative analysis using High-Performance Liquid Chromatography (HPLC).
Main Results:
- Peak plasma concentration (Cmax) of 1.68 microg/ml at 8 hours (tmax).
- Elimination half-life (t1/2) of 16.9 hours.
- Ravuconazole concentrations in lung and uterus were 2-6 times higher than plasma levels.
- Plasma to lung ratio exceeded that of other azoles.
Conclusions:
- Ravuconazole exhibits significant tissue penetration, particularly in the lung and uterus.
- Its favorable pharmacokinetic profile and broad antifungal spectrum suggest efficacy for deep-seated mycoses.
- Ravuconazole is a strong candidate for treating infections caused by Candida, Aspergillus, and Cryptococcus.