TABLE 1

Determination of IC50,u of individual human P450s for probe inhibitors

Results are expressed as the mean IC50 of duplicate determinations. The IC50 measurements were carried out as described under Materials and Methods. Because of the very low protein concentration used in the assays (∼0.01 mg/ml), fuinc approached unity for all the compounds (>0.8).


Compound

CYP1A2

CYP2B6

CYP2C8

CYP2C9

CYP2C19

CYP2D6

CYP3A4

CYP3A5
IC50,u (μM)
Propafenone 12 >50 >50 >50 11 0.02 9 30
Quinidine >50 >50 >50 >50 >50 0.02 19 4
Chlorpromazine 4 >50 >50 >50 9 0.3 2 42
Fluoxetine 90 >50 >50 20 0.3 0.7 10 >50
Norfluoxetine 14 14 >50 28 2 2 5 >50
Ritonavir 42 6 6 0.2 7 2 0.01 0.002
Sertraline 35 4 >50 41 1 2 9 18
Labetalol >50 61 35 >50 30 6 >50 94
Diphenhydramine >50 66 73 >50 88 6 55 >50
Amitriptyline 92 >50 >50 63 15 8 12 42
Fluvoxamine 0.1 8 >50 3 0.1 13 4 >50
Omeprazole 23 >50 >50 21 2 15 14 46
Diltiazem >50 >50 >50 >50 >50 23 10 67
Verapamil 123 >50 >50 74 >50 24 5 10
Mexiletine 17 >50 >50 >50 >50 25 >50 >50
Cimetidine
>50
>50
>50
>50
28
91
>50
>50