Inhibition of dextromethorphan O-demethylation and atomoxetine 4-hydroxylation in CYP2D6.1, CYP2D6.10, and CYP2D6.17
All reactions were run in duplicate. Error estimates are based on the best fit of the average values obtained at each point to the Michaelis-Menten equation using nonlinear regression analysis.
Inhibitor | Ki | Ki ratio | ||||||
|---|---|---|---|---|---|---|---|---|
| CYP2D6.1 | CYP2D6.10 | CYP2D6.17 | 2D6.10/2D6.1 | 2D6.17/2D6.1 | ||||
| μM | ||||||||
| Dextromethorphan O-demethylation | ||||||||
| Cocaine | 1.15 ± 0.14 | 1.74 ± 0.25 | 9.29 ± 1.13 | 1.51 | 8.08 | |||
| (S)-Fluoxetine | 1.27 ± 0.12 | 0.40 ± 0.05 | 1.73 ± 0.20 | 0.32 | 1.36 | |||
| (S)-Norfluoxetine | 0.84 ± 0.14 | 0.34 ± 0.05 | 1.84 ± 0.31 | 0.41 | 2.19 | |||
| Imipramine | 3.34 ± 0.28 | 3.70 ± 0.43 | 11.1 ± 0.8 | 1.11 | 3.32 | |||
| Quinidine | 0.011 ± 0.001 | 0.051 ± 0.003 | 0.079 ± 0.005 | 4.64 | 7.18 | |||
| Thioridazine | 0.018 ± 0.003 | 0.213 ± 0.017 | 0.166 ± 0.016 | 11.8 | 9.22 | |||
| Atomoxetine 4-hydroxylation | ||||||||
| Cocaine | 0.35 ± 0.04 | 0.43 ± 0.06 | 1.60 ± 0.21 | 1.23 | 4.57 | |||
| (S)-Fluoxetine | 0.67 ± 0.07 | 0.49 ± 0.09 | 0.82 ± 0.09 | 0.73 | 1.22 | |||
| (S)-Norfluoxetine | 1.04 ± 0.11 | 0.59 ± 0.11 | 1.16 ± 0.13 | 0.57 | 1.12 | |||
| Imipramine | 3.04 ± 0.34 | 4.26 ± 0.43 | 7.64 ± 0.64 | 1.40 | 2.51 | |||
| Quinidine | 0.010 ± 0.001 | 0.023 ± 0.002 | 0.056 ± 0.007 | 2.30 | 5.60 | |||
| Thioridazine | 0.026 ± 0.002 | 0.494 ± 0.090 | 0.103 ± 0.009 | 19.0 | 3.96 | |||