Estimation of the amount of atomoxetine and its metabolites from radioactivity in urine from CYP2D6 extensive and poor metabolizer subjects following oral administration of14C-atomoxetine3-a
| Percentage of Dose | ||
|---|---|---|
| CYP2D6 Poor Metabolizer Subjects | CYP2D6 Extensive Metabolizer Subjects | |
| Compound | ||
| 4-Hydroxy-N-desmethylatomoxetine | 3% | trace3-b |
| 4-Hydroxyatomoxetine | 6% | 3% |
| 2-Hydroxymethylatomoxetine | trace | trace |
| Hydroxyatomoxetine (1)3-c | trace | trace |
| Hydroxyatomoxetine (2)3-c | trace | trace |
| N-Desmethylatomoxetine | 1% | N.D. |
| 4-Hydroxy-N-desmethylatomoxetine-O-glucuronide | 2% | 3% |
| 4-Hydroxyatomoxetine-O-glucuronide | 31% | 84% |
| 2-Hydroxymethylatomoxetine-O-glucuronide | 2% | trace |
| Dihydroxyatomoxetine-O-glucuronide (1)3-c | 3% | N.D. |
| Dihydroxyatomoxetine-O-glucuronide (2)3-c | trace | trace |
| 4-Hydroxy-2-carboxyatomoxetine-O-glucuronide | 7% | trace |
| Hydroxy carboxyatomoxetine-O-glucuronide3-c | 4% | trace |
| Atomoxetine | 2% | 1% |
| Total defined | 61%3-d | 91% |
| Undefined | 15% | 5% |
| Dose recovered in urine3-e | 76% | 96% |
Data represent the mean metabolite or atomoxetine percentage of dose for EM and PM subjects.
N.D., not detected.
↵3-a Multiple 20-mg doses of atomoxetine were administered twice daily over 5 days followed by a single radiolabeled atomoxetine 20-mg dose (actual dose 19.66 mg; 92.4 μCi) on the morning of the 6th day.
↵3-b Trace indicates that although analyte was present, it was not quantifiable due to the amount of radioactivity associated with analyte peak.
↵3-c Specific hydroxylation sites for these metabolites have not been defined.
↵3-d In CYP2D6 PM subjects, the primary atomoxetine-derived metabolite was identified as 4-hydroxyatomoxetine-O-glucuronide in the remaining radioactivity recovered in the urine (120–264 h) and feces (0–264 h).
↵3-e Based on the amount of radioactivity recovered in urine from 0 to 120 h for PM and 0 to 168 h for EM subjects.