TABLE 1

Reversible inhibitory IC50 (± S.E.) values for PPP, thioTEPA, clopidogrel, and ticlopidine for several human P450 activities in pooled human liver microsomes




IC50
Enzyme
Activity
PPP
ThioTEPA
Clopidogrel
Ticlopidine
μM μM μM μM
CYP1A2 Phenacetin O-deethylase >300 >300 4.4 ± 0.1 12 ± 2
CYP2A6 Coumarin 7-hydroxylase >300 240 ± 30 0.046 ± 0.010 >300
CYP2B6 Bupropion hydroxylase 5.1 ± 0.1 8.3 ± 1.3 0.046 ± 0.01 0.21 ± 0.02
CYP2C8 Amodiaquine N-deethylase >300 >300 18 ± 2 100 ± 30
CYP2C9 Diclofenac 4′-hydroxylase >300 >300 21 ± 4 51 ± 19
CYP2C19 S-Mephenytoin 4′-hydroxylase >300 >300 3.7 ± 0.5 0.85 ± 0.09
CYP2D6 Dextromethorphan O-demethylase 74 ± 16 >300 200 ± 30 3.3 ± 0.2
CYP2E1 Chlorzoxazone 6-hydroxylase >300 >300 >300 >300
CYP3A Felodipine oxidase >300 >300 66 ± 13 >300
CYP3A Midazolam 1′-hydroxylase 200 ± 30 230 ± 60 34 ± 2 >300
CYP3A Testosterone 6β-hydroxylase >300 100 ± 40 23 ± 5 25 ± 4
Selectivity for CYP2B6

15
12
86
4