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  Content Director:  
Russell E. Lewis, Pharm.D. 
Russell E. Lewis, Pharm.D.  
Ravuconazole


Trade & Generic Names

Ravuconazole (formerly BMS-207147 and ER-30346) is a triazole structurally related to fluconazole and voriconazole. It is being developed by Bristol-Myers Squibb for oral use. Its trade name has not been announced.

ravuconazole structure

Mechanism(s) of Action

As with all azole antifungal agents, ravuconazole works principally by inhibition of cytochrome P450 14a-demethylase (P45014DM). This enzyme is in the sterol biosynthesis pathway that leads from lanosterol to ergosterol [2092]. The potency of ravuconazole to inhibit sterol C14 demethylation is similar to that of itraconazole [995].


Ravuconazole is active against Candida spp., Cryptococcus neoformans, Aspergillus fumigatus, dermatophytes and dematiaceous fungi [785]. It is slightly less potent against Candida tropicalis, Candida glabrata, and Candida krusei that against other Candida spp, but it appears likely that it will be clincally active against all these species of Candida [785, 1783].

The activity of ravuconazole against Sporothrix schenckii, Pseudallescheria boydii, Fusarium spp., and fungi belonging to zygomycetes order is limited [785, 994].

For ravuconazole MICs obtained for various types of fungi, see susceptibility patterns and the susceptibility database.

Usual Doses
No data are available from Phase I and ongoing Phase II clinical trials. Typical doses are not yet known.

Side-Effects

Results of the clinical trials in men have not yet been reported.

No side effects have been noted in rats and dogs who have been treated with ravuconazole for a week [1614].

Routes

Ravuconazole has only been described as an oral formulation thus far.

Current Status

Ravuconazole is currently in Phase II clinical trials.

Unfortunately, the drug has not advanced as of yet to Phase III trials.




References

785. Fung-Tomc, J. C., E. Huczko, B. Minassian, and D. P. Bonner. 1998. In vitro activity of a new orial triazole, BMS-207147 (ER-30346). Antimicrob. Agents Chemother. 42:313-318.

994. Hata, K., J. Kimura, H. Miki, T. Toyosawa, T. Nakamura, and K. Katsu. 1996. In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum. Antimicrob. Agents Chemother. 40:2237-2242.

995. Hata, K., J. Uneo, H. Miki, T. Toyosawa, K. Katsu, T. Nakamura, and T. Horie. 1995. ER-30346, a novel antifungal triazole: III. In vitro activity and its mode of action. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract No.

1614. Nakamura, T., R. Sakai, J. Sonoda, T. Katoh, T. Kaneko, and T. Horie. 1995. ER-30346, a novel antifungal triazole: IV. Pharmacokinetics and toxicological studies in mice, rats, and dogs. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract No.

1783. Pfaller, M. A., S. A. Messer, R. J. Hollis, R. N. Jones, G. V. Doern, M. E. Brandt, and R. A. Hajjeh. 1998. In vitro susceptibilities of Candida bloodstream isolates to the new triazole antifungal agents BMS-207147, Sch 56592, and voriconazole. Antimicrob. Agents Chemother. 42:3242-3244.

2092. Sheehan, D. J., C. A. Hitchcock, and C. M. Sibley. 1999. Current and emerging azole antifungal agents. Clin. Microbiol. Rev. 12:40-79.



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