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. 2015 Jun 12;59(7):3973–3983. doi: 10.1128/AAC.05035-14

TABLE 2.

Target total serum levels for therapeutic drug monitoring of voriconazole-amphotericin B combination therapy in relation to the MIC of the infecting isolatec

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
a

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.

b

The tCmin value was calculated by dividing fCmin by 0.42, the free fraction of voriconazole.

c

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.