IC50 values for mechanism-based inactivators of human P450 enzymes following a 30-min incubation with human liver microsomes in the absence and presence of NADPH
Inactivator | P450 | IC50 | IC50 Shift | ||
|---|---|---|---|---|---|
| Without NADPH | With NADPH | ||||
| μM | -fold difference | ||||
| Furafyllinea | CYP1A2 | 1.5 | 0.027 | 56 | |
| Zileuton | CYP1A2 | 41 | 2.9 | 14 | |
| PPP | CYP2B6 | 4.8 | 0.12 | 40 | |
| thioTEPA | CYP2B6 | 3.8 | 0.099 | 38 | |
| CYP2C8 | >1000 | 21 | >48 | ||
| CYP2C19 | >600 | 75 | >8 | ||
| CYP3A (midazolam) | 2.7 | 7.1 | 3.8 | ||
| CYP3A (testosterone) | 42 | 12 | 3.5 | ||
| Desethylamiodarone | CYP2B6 | 2.2 | 0.67 | 3.3 | |
| CYP2C8 | 2.0 | 0.68 | 2.9 | ||
| CYP2C9 | 2.6 | 0.47 | 5.5 | ||
| CYP2D6 | 3.1 | 0.64 | 4.8 | ||
| CYP3A (midazolam) | 4.8 | 1.6 | 3.0 | ||
| CYP3A (testosterone) | 1.8 | 0.76 | 2.4 | ||
| Tienilic acid | CYP2C9 | 0.43 | 0.027 | 16 | |
| Ticlopidine | CYP1A2 | 12 | 0.75 | 16 | |
| CYP2B6 | 0.13 | 0.031 | 4.2 | ||
| CYP2C19 | 0.63 | 0.33 | 1.9 | ||
| CYP3A (testosterone) | 48 | 18 | 2.7 | ||
| MDMA | CYP1A2 | >600 | 23 | >26 | |
| CYP2B6 | >900 | 56 | >16 | ||
| CYP2D6 | 4.2 | 0.046 | 91 | ||
| Paroxetine | CYP2D6 | 0.23 | 0.012 | 19 | |
| CYP3A (midazolam) | 15 | 4.8 | 3.1 | ||
| CYP3A (testosterone) | 19 | 6.5 | 2.9 | ||
| Diltiazem | CYP3A (midazolam) | 54 | 3.7 | 15 | |
| CYP3A (testosterone) | 55 | 1.8 | 31 | ||
| Erythromycin | CYP3A (midazolam) | 18 | 1.2 | 15 | |
| CYP3A (testosterone) | >600 | 0.72 | >830 | ||
| Ritonavir | CYP3A (midazolam) | 0.0044 | 0.0028 | 1.6 | |
| CYP3A (testosterone) | 0.0083 | 0.0040 | 2.1 | ||
| Verapamil | CYP3A (midazolam) | 12 | 0.12 | 100 | |
|
| CYP3A (testosterone) | 8.2 | 0.15 | 55 | |
↵ a Furafylline also showed inactivation of CYP2C19 and CYP2D6; however, solubility limitations prohibited the further examination of furafylline as an inactivator of these enzyme activities.