TABLE 2

IC50 values (μM) of ticlopidine, thioTEPA, metyrapone, xanthate C8, and benzylisothiocyanate on P450-specific model activities in human liver microsomes Mechanism-based inhibition experiments (15-min preincubation) for CYP2B6 are also presented. Substrate concentrations in parentheses.


P450 isoform

Substrate

Ticlopidine

ThioTEPA

Metyrapone

Xanthate C8

Benzyl-isothiocyanate
CYP1A1/2 Ethoxyresorufin (1 μM) 13.2 >1000 >100 307 5.6
CYP2A6 Coumarin (10 μM) 555 256 >100 4.8 25
CYP2B6 Bupropion (50 μM) 0.32/0.08 1.75/2.0 4.14/2.44 6.9/31.9 8.59/9.1
CYP2C9 Tolbutamide (200 μM) >1000 >1000 39.6 48 >100
CYP2C19 rac-Mephenytoin (100 μM) 2.7 >1000 >10 6.9 7.2
CYP2D6 Dextromethorphan (100 μM) 4.4 >1000 1.06 219 4.8
CYP2E1 Chlorzoxazone (100 μM) 749 >1000 >100 1.8 >1000
CYP3A4/5
Midazolam (10 μM)
>1000
556
2.58
393
31.5