In vitro inhibition of CYP3A, CYP2D6, CYP2C9, and CYP1A2 form-selective catalytic activities by atomoxetine, N-desmethylatomoxetine, and 4-hydroxyatomoxetine
Form Selective Catalytic Activity | Compound | Type of Inhibition | Ki Apparent |
|---|---|---|---|
| CYP3A | Atomoxetine | Mixed competitive/non-competitive | 34 ± 9 μM |
| Midazolam 1′-hydroxylation | N-Desmethylatomoxetine | Mixed competitive/non-competitive | 16 ± 1 μM |
| 4-Hydroxyatomoxetine | Non-competitive | 461 ± 32 μM | |
| CYP2D6 | Atomoxetine | Competitive | 3.6 ± 0.3 μM |
| Bufuralol 1′-hydroxylation | N-Desmethylatomoxetine | Competitive | 5.3 ± 0.2 μM |
| 4-Hydroxyatomoxetine | Competitive | 17 ± 1 μM | |
| CYP2C9 | Atomoxetine | Nonea | N.A. |
| Diclofenac 4′-hydroxylation | N-Desmethylatomoxetine | Competitive | 53 ± 3 μM |
| 4-Hydroxyatomoxetine | Nonea | N.A. | |
| CYP1A2 | Atomoxetine | Nonea | N.A. |
| Phenacetin O-deethylation | N-Desmethylatomoxetine | Mixed competitive/non-competitive | 271 ± 26 μM |
|
| 4-Hydroxyatomoxetine | Nonea | N.A. |
N.A., not applicable; ≤34% inhibition.
↵ a No significant inhibition in vitro was observed.