Venlafaxine (VEN) is mainly metabolized via CYP2D6 to O-desmethylvenlafaxine (ODV) and by CYP3A4 to N-desmethylvenlafaxine (NDV). CYP2C19 is also involved in the formation of ODV; CYP2C19 activity has been reported to be inhibited to a different extend by omeprazole and pantoprazole. Aim of our study was to analyze the in vivo pharmacokinetic interaction potential between venlafaxine and two PPIs based upon therapeutic drug monitoring (TDM).
1765 patients out of a TDM database of 4000 venlafaxine-medicated patients were stratified in three groups: a control group without a concomitant PPI (VC, n = 1685), a group co-medicated with pantoprazole (VP, n = 40) and one group co-medicated with omeprazole (VO, n = 40). We compared plasma concentrations of VEN, ODV, and the active moiety, AM, (VEN+ODV) between groups with the Kruskal-Wallis-Test. Mann-Whitney U test was used to control for significant differences between pairs of groups with regard to the distributions.
Median daily dosage of VEN groups didn't differ between groups. Plasma concentrations for ODV, VEN+ODV in the VO group and VEN+ODV in the VP group were significantly higher than in the control group (p = 0.001 and p = 0.017 for Mann-Whitney U Test; p = 0.019 for Mann-Whitney U Test).
The addition of the PPI pantoprazole or omeprazole to an ongoing venlafaxine treatment may substantially influence the metabolism of venlafaxine leading in elevated VEN+ODV concentrations. Enhanced ODV concentrations in the VO group imply a strong inhibiting effect of omeprazole on CYP2C19-mediated metabolism of venlafaxine to NDV and instead to a higher proportion of ODV via CYP2D6.
