TABLE 3

P450 activity of human hepatocytes suspended in human plasma in the presence of ketoconazole Ketoconazole was equilibrated with human hepatocytes in human plasma to allow nonspecific binding. After equilibration, the extracellular concentration of ketoconazole was measured. The remaining P450 activities in hepatocytes (fA) were also determined using the probe substrates.

Ketoconazole
fA
In Incubation
Extracellular
CYP1A2
CYP2C9
CYP2C19
CYP2D6
CYP3A4
μM %
100 71.8 79 60 32 96 0
50 34.0 81 71 42 84 0
25 14.1 83 72 57 99 0
12.5 7.30 89 75 63 91 1
6.25 4.04 92 80 83 99 5
3.13 2.22 92 84 90 100 11
1.56 0.857 97 79 89 97 12
0
0
100
100
100
100
100

  • fA, % fraction of enzyme activity remaining in the presence of ketoconazole inhibition (%)