Effect of ETT on some P450 enzyme activities in human liver microsomes
P450 | Enzyme Activity | Control Ratea,b | ETT IC50c |
|---|---|---|---|
| pmol/min/mg protein | μM | ||
| CYP1A2 | 7-Ethoxyresorufin O-deethylase | 39 | >100 |
| CYP2B6 | S-Mephenytoin N-demethylase | 14 | >100 |
| CYP2C9 | Tolbutamide methylhydroxylase | 98 | >100 |
| CYP2C19 | S-Mephenytoin 4′-hydroxylase | 4.1 | >100 |
| CYP2D6 | Debrisoquine 4-hydroxylase | 60 | 84 |
| CYP2E1 | Chlorzoxazone 6-hydroxylase | 400 | >100 |
| CYP3A4 | Testosterone 6β-hydroxylase | 819 (836, 802) | 95 (87, 100) |
|
CYP3A4
|
Testosterone 6β-hydroxylase (mechanism-based inhibition)
|
723 (760, 685)
|
40 (38, 42)
|
↵ a Enzyme activity in the absence of added ETT.
↵ b Incubations were performed with the pool II human liver microsomal preparation, except for testosterone 6β-hydroxylase, where both the pool I and II human liver microsomal preparations were used.
↵ c The effect of ETT on the P450 enzyme activities was determined over a concentration range of up to 100 μM.