FIG 3 .
Pharmacodynamic index studies for Aspergillus fumigatus strain 16216, which is the same TR34/L98H mutant used in the experiment whose results are shown in Fig. 2. The pharmacodynamic data presented in Fig. 2 have been transformed from dose (mg/kg) to different pharmacodynamic indices. Two pharmacodynamic endpoints are used: the GM at the end of the experiment and the area under the GM-time curve. (A and B) The data suggest there is no relationship between Cmax/MIC and the observed antifungal effect. (C and D) Similarly, the data suggest there is no relationship between AUC/MIC and the observed antifungal effect. (E to H) In contrast, there is a striking relationship between the total drug Cmin/MIC versus effect (E and F), as well as the fractions of the dosing interval plasma concentrations that are >1 mg/liter and the antifungal effect (G and H). These analyses suggest that there is a strong threshold effect (or time-dependent) antifungal activity that is exhibited by F901318.