TABLE 1

Inhibition of the major P450 enzymes in human liver microsomes by gemfibrozil and its 1-O-β-glucuronide




IC50a
Enzyme P450 Reaction Gemfibrozil
Gemfibrozil Glucuronide


No Preincubation
30-min Preincubation
No Preincubation
30-min Preincubation
μM μM
CYP1A2 Phenacetin O-deethylation 99 ± 12 84 ± 6 250 ± 40 >300
CYP2B6 Bupropion hydroxylation >300 >300 >300 >300
CYP2C8 Paclitaxel 6α-hydroxylation 120 ± 20 150 ± 20 24 ± 5 1.8 ± 0.5
CYP2C9 Diclofenac 4′-hydroxylation 30 ± 2 30 ± 3 >300 >300
CYP2C19 S-Mephenytoin 4′-hydroxylation 100 ± 10 82 ± 18 >300 >300
CYP2D6 Dextromethorphan O-demethylation >300 >300 >300 >300
CYP3A4/5 Testosterone 6β-hydroxylation >300 >300 >300 >300
CYP3A4/5
Midazolam 1′-hydroxylation
>300
>300
>300
>300
  • a Values are displayed to two significant figures, ± standard error.