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Evaluation of voriconazole pharmacodynamics using time-kill methodology
M E Klepser1, D Malone, R E Lewis
1University of Iowa Colleges of Pharmacy, Iowa City, Iowa 52242, USA. michael-klepser@uiowa.edu
Antimicrobial Agents and Chemotherapy
|June 20, 2000
Summary
Voriconazole demonstrates fungistatic activity against Candida and Cryptococcus species. Its effectiveness plateaus, indicating non-concentration-dependent pharmacodynamics in vitro.
Area of Science:
- Mycology
- Pharmacology
- Antimicrobial Agents
Background:
- Voriconazole is an investigational azole antifungal with broad-spectrum activity.
- It is effective against various Candida species and Cryptococcus neoformans, including fluconazole-resistant strains.
Purpose of the Study:
- To characterize the relationship between voriconazole concentrations and its fungistatic activity.
- To evaluate the time- and concentration-dependent pharmacodynamics of voriconazole in vitro.
Main Methods:
- In vitro time-kill assays were performed.
- Fungal isolates (Candida albicans, Candida glabrata, Candida tropicalis, C. neoformans) were exposed to voriconazole concentrations from 0.0625 to 16 times the MIC.
- Viable colony counts were determined over 8, 12, and 24 hours.
- The 50% and 90% effective concentrations (EC50 and EC90) were calculated.
Main Results:
- Near-maximal fungistatic activity (EC90) was achieved at approximately three times the MIC.
- EC50 and EC90 values remained consistent over the tested time points (8, 12, and 24 hours).
- Increasing voriconazole concentrations beyond a certain point did not enhance the rate of antifungal activity.
Conclusions:
- Voriconazole exhibits non-concentration-dependent pharmacodynamic characteristics in vitro.
- The study suggests that the rate of voriconazole's antifungal activity is not improved by increasing concentrations.
- These findings are crucial for understanding voriconazole's efficacy and optimizing antifungal therapy.