Metabolism of Duloxetine, a New Antidepressant

Duloxetine, a reuptake inhibitor of both norepinephrine and serotonin, has been scheduled for release in the U.S. this year. In a 2-part, manufacturer-funded study, researchers . . .

Duloxetine, a reuptake inhibitor of both norepinephrine and serotonin, has been scheduled for release in the U.S. this year. In a 2-part, manufacturer-funded study, researchers investigated the role of duloxetine as both a substrate and an inhibitor of cytochrome P450 2D6 (CYP2D6). All study participants were extensive CYP2D6 metabolizers.

First, 14 healthy subjects (7 men) took single doses of a CYP2D6 substrate (desipramine, 50 mg) both alone and after reaching a steady state of duloxetine (taken as 60 mg twice daily). Compared with baseline measures, duloxetine increased desipramine's maximum concentration (C_max) and area under the time/concentration curve (AUC; a measure of drug exposure) 1.7 and 2.9 times, respectively. In a second stud…

Reviewing Author

Steven Dubovsky, MD