TABLE 1

Effect of fluconazole on P450 activity in human hepatocytes suspended in human plasma Fluconazole was equilibrated with human hepatocytes in human plasma to allow non-specific binding. After equilibration, the extracellular concentration of fluconazole was measured. The remaining P450 activities in hepatocytes (fA) were also determined using the probe substrates.

Total Fluconazole in Incubation
Fluconazole Extracellular
fA
CYP1A2
CYP2C9
CYP2C19
CYP2D6
CYP3A4
μM %
100 μM 98.4 91.9 21.2 10.6 74.2 15.4
50 μM 47.2 112 36.8 14.9 97.6 23.3
25 μM 26.5 89.5 55.2 27.8 102 34.9
12.5 μM 13.1 97.5 66.3 45.2 87.4 39.8
6.25 μM 6.10 90.8 78.9 64.7 115 50.6
3.13 μM 3.13 85.1 86.7 75.7 110 59.9
1.56 μM 1.46 90.0 89.3 89.2 89.0 66.7
0 μM
0
100
100
100
100
100