Inhibitory effects of GFZ (IC50, μM) and ketoconazole (percentage of inhibition at 1 μM concentration) on glucuronidation and oxidation of statins in human liver microsomes
| Gemfibrozil | Ketoconazole | ||
|---|---|---|---|
| IC50 | Inhibition | ||
| μM | % | ||
| SVA | Glucuronidation | 354 | |
| Oxidation | >800 | >85 | |
| AVA | Glucuronidation | 316 | |
| Oxidation | >750 | >90 | |
| CVA | Glucuronidation | 82 | |
| Oxidation (M1) | 87 | 68 | |
| Oxidation (M2) | 220 | ∼50 |
Incubations were performed in triplicate for each concentration of inhibitors, and involved coincubation of GFZ or ketoconazole with statins (10 μM) in the presence of NADPH (oxidation) or UDPGA (glucuronidation).