CYP2D6 Status of Extensive Metabolizers After Multiple-Dose Fluoxetine, Fluvoxamine, Paroxetine, or Sertraline

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Abstract
The aim of this study was to evaluate the CYP2D6 inhibitory effects of four selective serotonin reuptake inhibitors (SSRIs).Thirty-one healthy subjects were phenotyped as extensive metabolizers using the dextromethorphan/dextrorphan (DM/DX) urinary ratio as a marker for CYP2D6 activity before and after 8 days of administration of fluoxetine 60 mg (loading dose strategy), fluvoxamine 100 mg, paroxetine 20 mg, or sertraline 100 mg in a parallel-group design. Statistical analysis was performed on log-transformed DM/DX ratios because of variability within and between treatment groups. DM/DX ratios before (DM/DXBL) and after (DM/DXSSRI) were compared within and between the four SSRI groups. DM/DXBL ratios were not significantly different between the four SSRI treatment groups. Comparing within groups, significant differences between DM/DXBL and DM/DXSSRI were found for the fluoxetine (p SSRI