TABLE 2.
Drug and MIC (mg/liter) | Amphotericin B tCmaxa/voriconazole tCminb | Amphotericin B tCmaxa/voriconazole tCminb for isolates with a voriconazole MIC of: |
|||||
---|---|---|---|---|---|---|---|
0.25 mg/liter | 0.5 mg/liter | 1 mg/liter | 2 mg/liter | 4 mg/liter | 8 mg/liter | ||
Voriconazole | 0/0.45 | 0/0.9 | 0/1.8 | 0/3.6 | 0/7.2 | 0/14.4 | |
Amphotericin B | |||||||
0.25 | 0.7/0 | 0.125/0.275 | 0.125/0.55 | 0.125/1.1 | 0.125/2.2 | 0.125/4.4 | 0.125/8.8 |
0.5 | 1.4/0 | 0.25/0.275 | 0.25/0.55 | 0.25/1.1 | 0.25/2.2 | 0.25/4.4 | 0.25/8.8 |
1 | 2.8/0 | 0.5/0.275 | 0.5/0.55 | 0.5/1.1 | 0.5/2.2 | 0.5/4.4 | 0.5/8.8 |
2 | 9.3/0 | 1/0.275 | 1/0.55 | 1/1.1 | 1/2.2 | 1/4.4 | 1/8.8 |
4 | >10/0 | 2/0.275 | 2/0.55 | 2/1.1 | 2/2.2 | 2/4.4 | 2/8.8 |
The tCmax value was calculated by dividing fCmax by 0.05, 0.03, and 0.01, the free fractions of amphotericin B at tCmax <5, 5 to 10, and >10 mg/liter concentrations, respectively (19). Amphotericin B trough levels can be calculated by dividing the tCmin by 8, since the tCmax/trough ratio found in the present and other clinical studies is approximately 8.
The tCmin value was calculated by dividing fCmin by 0.42, the free fraction of voriconazole.
Underlined numbers correspond to concentrations associated with toxicity. The first row and column correspond to target values of voriconazole and amphotericin B monotherapy regimens, respectively.