Evaluation of voriconazole pharmacodynamics using time-kill methodology

Voriconazole is an investigational azole antifungal agent with activity against a variety of fungal species, including fluconazole-susceptible and -resistant Candida species and Cryptococcus neoformans, In this study, we employed in vitro time-kill methods to characterize the relationship between concentrations of voriconazole and its fungistatic activity against Candida albicans, Candida glabrata, Candida tropicalis, and C. neoformans. Isolates were exposed to voriconazole concentrations ranging from 0.0625 to 16 times the MIC, and the viable colony counts were determined over time. The 50 and 90% effective concentrations (EC50 and EC90, respectively) were determined at 8, 12, and 24 h following the addition of voriconazole, At each time point, near-maximal fungistatic activity, as indicated by the EC90, was noted at a drug concentration of approximately three times the MIC. Additionally, EC50 and EC90 did not change over time, thus suggesting that the rate of activity was not improved by increasing concentrations. Voriconazole exhibits non-concentration-dependent pharmacodynamic characteristics in vitro.