Abstract
Objectives: Venlafaxine is metabolized by CYP2D6 to O-desmethylvenlafaxine (ODV) and by CYP3A4 to N-desmethylvenlafaxine (NDV). CYP2C19 is also involved in the formation of ODV. The PPIs omeprazole and pantoprazole inhibit CYP2C19 to a different extent. Aim of this study was to investigate the potential effects of both PPIs on serum levels of VEN and ODV.
Methods: From a therapeutic drug monitoring (TDM) database, serum concentrations of VEN, ODV and the active moiety (VEN + ODV), were analyzed. Data from 120 patients were available and splitted into three groups: patients without PPI [noPPI], with pantoprazole [PANTO] or with omeprazole [OMEP] (n=40 each). The ratio of (ODV/VEN) was calculated as a marker of the metabolizer status.
Results: Median test detected no differences regarding the median daily dosage of VEN between the three groups (p=0.995); the mean daily doses for VEN were 207.6mg/d, SD=79.96 in the control-group, 209.06mg/d, SD=78.24 for the pantoprazole group and 203.43mg/d, SD=91.41 for omeprazole group. Plasma concentrations for VEN + ODVEN in the PANTO group were significantly higher than in the control group (p=0.019 for Mann-Whitney U Test). Plasma concentrations for ODVEN and VEN + ODVEN in the OMEP group were significantly higher than in the control group (p=0.001 and p=0.017 for Mann-Whitney U Test)
Conclusion: Both, omeprazole and pantoprazole led to a varying extent in increases of the serum concentrations of the active moiety (sum of VEN+ODV). The increase is driven by significantly higher levels of ODV in the OMEP group. This might be due to distinct CYP2C19 blocking properties of both PPIs, hindering the 2C19 mediated metabolization of VEN to N-desmethylvenlafaxine (NDV).