Figure legends
Figure 1. (a) 4-hour dextromethorphan/dextrorphan individual urinary metabolic ratios (UMRDEM/DOR) at baseline (control session) and after inhibition by paroxetine (inhibition session), following intake of dextromethorphan 5 mg per os (P < 0.0001). Ultrarapid metabolizers (gAS > 2, n = 4) are shown in red and extensive metabolizers (1 ≤ gAS ≤ 2, n = 33) in blue. Error bars represent the standard deviations of log-transformed UMRDEM/DOR. (b) Correlation between 4-hour log-transformed dextromethorphan/dextrorphan urinary metabolic ratios (log(UMRDEM/DOR)) and the CYP2D6 activity score (n = 43) with whiskers indicating the 10th and 90th percentiles (P < 0.0001)
Figure 2. Flowchart of the non-targeted metabolomics approach to identify biomarkers reflecting CYP2D6 activity. N represents the number of metabolic features after each step with plasma biomarkers in red and urinary biomarkers in yellow
Figure 3. Targeted Selected Ion Monitoring/data-dependent-MS2 of all features of interest in ESI+ mode
Figure 4. Log(area/creatinine) in urine off all CY2D6 biomarkers identified in metabolomics analyses measured with product ion monitoring (a) before and after paroxetine intake, including means and standard deviations on each side. Ultrarapid metabolizers (n = 4) are shown in red and extensive metabolizers (n = 33) in blue.(b) EM-UM subjects (n = 37) versus PM subjects (n = 6) with whiskers indicating the 10th and 90th percentiles. (c) Correlation with log(UMRDEM/DOR). Control session (n = 43) is represented by square and inhibition session (n = 42) by triangle. (d)Correlation with CYP2D6 activity score score ( n = 43) with whiskers indicating the 10th and 90thpercentiles. All P < 0.0001
Figure 5 . Log(area) in plasma off all CY2D6 biomarkers identified in metabolomics analyses measured with product ion monitoring (a) before and after paroxetine intake, including means and standard deviations on each side. Ultrarapid metabolizers (n = 4) are shown in red and extensive metabolizers (n = 33) in blue. (b) EM-UM subjects (n = 37) versus PM subjects (n = 6) with whiskers indicating the 10th and 90th percentiles. (c) Correlation with log(UMRDEM/DOR). Control session (n = 43) is represented by square and inhibtion session (n = 42) by triangle. (d) Correlation with CYP2D6 activity score (n = 43) with whiskers indicating the 10th and 90th percentiles. All P < 0.0001
Figure 6. Log(area/creatinine) or log(area) at baseline (control session) and after inhibition by paroxetine (inhibition session) (n = 5). On each side means values and standard deviations.