TABLE 1

fuinc, IC50, apparent, and IC50, unbound values determined in rCYP2C9 and human hepatocytes

Results are expressed as the mean IC50 of triplicate determinations. The IC50 measurements were carried out using diclofenac as the substrate as described under Materials and Methods. fuinc was determined under the same conditions as for the inhibition experiment.


Compound

IC50, apparent

fuinc

IC50, unbound
rCYP2C9
Human Hepatocytes
rCYP2C9
Human Hepatocytes
rCYP2C9
Human Hepatocytes
μM μM
Amiodarone 4 500 0.01 0.001 0.04 0.5
Benzbromarone 0.04 1.2 0.95 0.03 0.04 0.04
Clotrimazole 0.1
Diclofenac 12a 1 0.44 12
Fluconazole 16 60 1 0.86 16 52
Fluvastatin 2 6.7 1 0.2 2 1.3
Ibuprofen 159 1 0.62 159
Ketoconazole 6 0.95 0.35 11
4-Methylimidazole 117
Miconazole 0.04 19 0.52 0.03 0.02 0.6
Piroxicam 32
Quinine 243 500
Sertraline 48 118 0.62 0.22 30 26
Sulfaphenazole 0.4 0.6 1 1 0.4 0.6
Sulfamethiazole 259 463 1 1 259 463
Sulfinpyrazone 213 1000 1 0.19 213 190
Tolbutamide 244 1 1 244
Warfarin 12 13
Zafirlukast
0.5
29
1
0.04
0.5
1.1
  • a IC50 determined using naproxen as substrate.