Inhibition of CYP2D6-catalyzed bufuralol 1′-hydroxylase by fluoxetine, ezlopitant, imipramine, and quinidine with varying microsomal protein and phospholipid concentrations
| Inhibition Constant (IC50) | ||||
|---|---|---|---|---|
| Fluoxetine | Ezlopitant | Imipramine | Quinidine | |
| μM | ||||
| Control | 1.3 (0.3) | 0.57 (0.14) | 7.3 (0.8) | 0.018 (0.003) |
| Microsomal protein concentration (mg/ml) | ||||
| 0.2 | 2.4 (0.5) | 1.8 (0.5) | 5.4 (1.2) | 0.015 (0.003) |
| 0.5 | 3.5 (0.5) | 2.5 (1.2) | 3.9 (0.9) | 0.015 (0.003) |
| 2.0 | 7.3 (0.6) | 5.0 (1.4) | 14 (2) | 0.012 (0.002) |
| Phospholipid concentration (mg/ml) | ||||
| 0.2 | 2.7 (0.1) | 1.7 (0.4) | 5.7 (0.3) | 0.025 (0.003) |
| 0.5 | 4.2 (0.5) | 3.3 (0.8) | 6.4 (1.0) | 0.026 (0.005) |
| 2.0 | 21 (7) | 18 (3) | 16 (3) | 0.038 (0.006) |
Incubations were conducted at a bufuralol concentration of 10 μM. Control values represent inhibition in the presence of no additional protein or phospholipid. Microsomal protein concentration in the control was 0.0088 mg/ml. Assays were conducted in duplicate. Each value represents the mean with standard errors in parentheses.