Table 3

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 SubjectsCYP2D6 Extensive Metabolizer Subjects
 Hydroxyatomoxetine (1)3-c tracetrace
 Hydroxyatomoxetine (2)3-c tracetrace
 Dihydroxyatomoxetine-O-glucuronide (1)3-c 3%N.D.
 Dihydroxyatomoxetine-O-glucuronide (2)3-c tracetrace
 Hydroxy carboxyatomoxetine-O-glucuronide3-c 4%trace
Total defined61%3-d 91%
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.