ArticleClinical pharmacokinetics2018
Effects of the Proton Pump Inhibitors Omeprazole and Pantoprazole on the Cytochrome P450-Mediated Metabolism of Venlafaxine.
Article in Clinical pharmacokinetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.
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Who cites it
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- Venlafaxine's therapeutic reference range in the treatment of depression revised: a systematic review and meta-analysis.Psychopharmacology · 2024Pooled it
- A Systematic Review of Gastric Acid-Reducing Agent-Mediated Drug-Drug Interactions with Orally Administered Medications.Clinical pharmacokinetics · 2020Pooled it
- Psychopharmacological Mechanisms of Antidepressant Withdrawal: Insights From Venlafaxine.Human psychopharmacology · 2026Review
- [Metamizole / dipyrone in psychiatry - What about the pharmacokinetics?]Der Nervenarzt · 2025Review
- The Effect of Concomitant Administration of Proton Pump Inhibitors on the Pharmacokinetics of CDK4/6 Inhibitors in Rats: Implications for the Evaluation of Hepatic and Transporter-Mediated Drug-Drug Interactions.European journal of drug metabolism and pharmacokinetics · 2024Article
- Estimation of CDK inhibitors by RP-HPLC: application for pharmacokinetic interactions studies with PPIs.Bioanalysis · 2024Article
- Lower sertraline plasma concentration in patients co-medicated with clozapine-Implications for pharmacological augmentation strategies in schizophrenia.Pharmacology research & perspectives · 2023Article
- Current Status of Therapeutic Drug Monitoring in Mental Health Treatment: A Review.Pharmaceutics · 2022Review
- Subtherapeutic bupropion and hydroxybupropion serum concentrations in a patient with CYP2C19*1/*17 genotype suggesting a rapid metabolizer status.The pharmacogenomics journal · 2020Article
- In Vitro and In Vivo Rat Model Assessments of the Effects of Vonoprazan on the Pharmacokinetics of Venlafaxine.Drug design, development and therapy · 2020Article
- Pharmacokinetics of venlafaxine in treatment responders and non-responders: a retrospective analysis of a large naturalistic database.European journal of clinical pharmacology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveAn increasing trend in prescribing proton pump inhibitors (PPIs) inevitably increases the risk of unwanted drug-drug interactions (DDIs). The aim of this study was to uncover pharmacokinetic interactions between two PPIs-omeprazole and pantoprazole-and venlafaxine.
methodsA therapeutic drug monitoring database contained plasma concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine. We considered three groups: a group of patients who received venlafaxine without confounding medications (non-PPI group, n = 906); a group of patients who were comedicated with omeprazole (n = 40); and a group of patients comedicated with pantoprazole (n = 40). Plasma concentrations of venlafaxine, O-desmethylvenlafaxine and active moiety (venlafaxine + O-desmethylvenlafaxine), as well as dose-adjusted plasma concentrations, were compared using non-parametrical tests.
resultsDaily doses of venlafaxine did not differ between groups (p = 0.949). The Mann-Whitney U test showed significantly higher plasma concentrations of active moiety, as well as venlafaxine and O-desmethylvenlafaxine, in both PPI groups [p = 0.023, p = 0.011, p = 0.026, +29% active moiety, +27% venlafaxine, +36% O-desmethylvenlafaxine (pantoprazole); p = 0.003, p = 0.039 and p < 0.001, +36% active moiety, +27% venlafaxine, +55% O-desmethylvenlafaxine (omeprazole)]. Significantly higher concentration-by-dose (C/D) values for venlafaxine and active moiety were detected in the pantoprazole group (p = 0.013, p = 0.006, respectively), while in the omeprazole group, C/D ratios for all three parameters-venlafaxine, O-desmethylvenlafaxine and active moiety-were significantly higher (p = 0.021, p < 0.001 and p < 0.001, respectively).
conclusionsSignificantly higher plasma concentrations for all parameters (venlafaxine, O-desmethylvenlafaxine, active moiety) suggest clinically relevant inhibitory effects of both PPIs, most likely on the cytochrome P450 (CYP) 2C19-mediated metabolism of venlafaxine. The findings might be the result of different degrees of CYP2C19 involvement, therefore the inhibition of CYP2C19 by both PPIs may lead to an increased metabolism via CYP2D6 to O-desmethylvenlafaxine.
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