TABLE 4

Duloxetine metabolites in urine analyzed from 0 to 72 h expressed as individual and mean percentage of total dose


Compound

Total % of Dose (0-72 h)a

Mean % of Total Dose (0-72 h, n = 4)
Subject 1
Subject 2
Subject 3
Subject 4
Glucuronide conjugate of dihydrodiol duloxetine (M1) 1.7 N.D. 0.4 0.7 0.7
Dihydrodiol duloxetine (M2) 3.8 1.2 0.6 2.2 1.9
Glucuronide conjugate of 5-hydroxy-6-methoxy duloxetine (M3) 2.3 1.1 2.0 1.1 1.6
Glucuronide conjugate of 5-hydroxy duloxetine (M4) 0.9 1.0 0.4 N.D. 0.6
Glucuronide conjugate of dihydroxy duloxetine (M5)b 2.6 1.5 2.4 2.7 2.3
Glucuronide conjugate of 4-hydroxy duloxetine (M6) 13.2 21.4 17.5 15.5 16.9
Sulfate conjugate of 5-hydroxy-6-methoxy duloxetine (M7) 9.7 10.5 16.2 13.5 12.5
Glucuronide conjugate of 6-hydroxy duloxetine (M8) 1.6 1.7 2.6 2.2 2.0
Glucuronide conjugate of 4,6-dihydroxy duloxetine (M9)b 5.7 2.5 5.1 3.7 4.3
Glucuronide conjugate of 6-hydroxy-5-methoxy duloxetine (M10) 4.1 3.5 6.4 6.2 5.0
Sulfate conjugate of 4-hydroxy duloxetine (M11) 4.1 3.5 6.4 6.2 5.0
Sum of the mean % identified metabolites over 72 h: 52.9
Mean % recovery of radioactivity excreted in urine over 72 h:




67.9
  • N.D., the metabolite was not detected by HPLC/radiochemical detection

  • a Urine samples were not analyzed past 72 h post dose due to low amounts of radioactivity. Results are based on 84% extraction efficiency

  • b This compound exists in different isomeric forms that show different retention times on HPLC, but have the same mass