Trial reportEuropean journal of clinical pharmacology2008
Inhibition of metoprolol metabolism and potentiation of its effects by paroxetine in routinely treated patients with acute myocardial infarction (AMI).
Trial report in European journal of clinical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 5 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 5 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Clinical Pharmacokinetics of Metoprolol: A Systematic Review.Clinical pharmacokinetics · 2022Pooled it
- CYP2D6 polymorphism and its impact on the clinical response to metoprolol: A systematic review and meta-analysis.British journal of clinical pharmacology · 2020Pooled it
- The impact of CYP2D6 mediated drug-drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine.British journal of clinical pharmacology · 2018Pooled it
- Pooled it
- Pooled it
- Influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine.Journal of clinical pharmacology · 2011Trial
- Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone.British journal of clinical pharmacology · 2010Trial
- CYP2D6 is a major determinant of metoprolol disposition and effects in hospitalized Russian patients treated for acute myocardial infarction.European journal of clinical pharmacology · 2008Trial
- CYP2D6-inhibiting drugs and risk of fall injury after newly initiated therapy with beta-blockers-a register-based case-crossover study.Scientific reports · 2025Article
- Co-prescription of metoprolol and CYP2D6-inhibiting antidepressants before and after implementation of an optimized drug interaction database in Norway.European journal of clinical pharmacology · 2022Article
- Impact of theFrontiers in pharmacology · 2022Article
- Discontinuation and dose adjustment of metoprolol after metoprolol-paroxetine/fluoxetine co-prescription in Dutch elderly.Pharmacoepidemiology and drug safety · 2018Article
- MicroRNA hsa-miR-370-3p suppresses the expression and induction of CYP2D6 by facilitating mRNA degradation.Biochemical pharmacology · 2017Article
- Risk of emergent bradycardia associated with initiation of immediate- or slow-release metoprolol.Pharmacotherapy · 2013Article
- Is antiarrhythmic treatment in the elderly different? a review of the specific changes.Drugs & aging · 2011Review
- Cytochrome P450-2D6 Genotype Definition May Improve Therapy for Paroxysmal Atrial Fibrillation A Case of Syncope Following "Pill-in-the-Pocket" Quinidine plus Propafenone.Journal of atrial fibrillationArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo investigate the influence of paroxetine on metoprolol concentrations and its effect in patients treated for acute myocardial infarction (AMI) who are routinely given paroxetine as a co-treatment of depression.
methodsWe recruited 17 depressed AMI patients who received metoprolol as a routine part of their therapy (mean dose 75 +/- 39 mg/day). Patients were genotyped for CYP2D6 3, 4 and gene duplication. Metoprolol and alpha-hydroxy-metoprolol were analyzed in plasma 0, 2, 6 and 12 h post-dose. Heart rates (HR) at rest were registered after each sampling. Paroxetine 20 mg daily was then administered, and all measurements were repeated on day 8.
resultsAll patients were genotypically extensive metabolizers (EMs) (nine with 1/1 and eight with 1/3 or 4). Following the administration of paroxetine, mean metoprolol areas under the concentration-time curve (AUC) increased (1064 +/- 1213 to 4476 +/- 2821 nM x h/mg per kg, P = 0.0001), while metabolite AUCs decreased (1492 +/- 872 to 348 +/- 279 n M x h/mg per kg, P < 0.0001), with an increase of metabolic ratios (MR) (0.9 +/- 1.3 to 26 +/- 29; P < 0.0001). Mean HRs were significantly lower after the study week at each time point. Mean area under the HR versus time curve (AUEC) decreased (835 +/- 88 to 728 +/- 84 beats x h/min; P = 0.0007). Metoprolol AUCs correlated with patients' AUECs at the baseline (Spearman r = -0.64, P < 0.01), but not on the eighth day of the study. A reduction of metoprolol dose was required in two patients due to excessive bradycardia and severe orthostatic hypotension. No other adverse effects of the drugs were identified.
conclusionA pronounced inhibition of metoprolol metabolism by paroxetine was observed in AMI patients, but without serious adverse effects. We suggest, however, that the metoprolol dose is controlled upon initiation and withdrawal of paroxetine.
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