Trial reportEuropean journal of clinical pharmacology2008
CYP2D6 is a major determinant of metoprolol disposition and effects in hospitalized Russian patients treated for acute myocardial infarction.
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 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- CYP2D6 polymorphism and its impact on the clinical response to metoprolol: A systematic review and meta-analysis.British journal of clinical pharmacology · 2020Pooled it
- Differential outcomes from metabolic ratios in the identification of CYP2D6 phenotypes--focus on venlafaxine and O-desmethylvenlafaxine.European journal of clinical pharmacology · 2010Pooled it
- Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype-Derived Activity Scores.CPT: pharmacometrics & systems pharmacology · 2020Trial
- Effect of metoprolol exposure following myocardial infarction on future cardiovascular events: a Mendelian randomization study.European journal of clinical pharmacology · 2025Article
- The role of pharmacogenomics in contemporary cardiovascular therapy: a position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.European heart journal. Cardiovascular pharmacotherapy · 2022Article
- Physiologically Based Pharmacokinetic Modeling of Metoprolol Enantiomers and α-Hydroxymetoprolol to Describe CYP2D6 Drug-Gene Interactions.Pharmaceutics · 2020Article
- Pharmacogenetic factors affecting β-blocker metabolism and response.Expert opinion on drug metabolism & toxicology · 2020Review
- Prescribed Doses of CYP2D6-Metabolized Drugs and Hemodynamic Responses in Relation to CYP2D6 Genotype Among Older Patients Exposed to Polypharmacy.Drugs & aging · 2020Article
- Pharmacogenomic considerations for medications in the perioperative setting.Pharmacogenomics · 2019Review
- Extracorporeal circulation systems in coronary artery bypass surgery can affect pharmacokinetics of drugs: may altered CYP-mediated liver function be a possible reason?European journal of clinical pharmacology · 2018Article
- Pharmacogenomics of Medications Commonly Used in the Intensive Care Unit.Frontiers in pharmacology · 2018Review
- CYP2D6 Genetic Variation and Beta-Blocker Maintenance Dose in Patients with Heart Failure.Pharmaceutical research · 2017Article
- Precision Cardiovascular Medicine: State of Genetic Testing.Mayo Clinic proceedings · 2017Review
- Multiplex SNaPshot-a new simple and efficient CYP2D6 and ADRB1 genotyping method.Human genomics · 2016Article
- Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population.Patient preference and adherence · 2016Article
- G protein-coupled receptor kinase 5 gene polymorphisms are associated with postoperative atrial fibrillation after coronary artery bypass grafting in patients receiving β-blockers.Circulation. Cardiovascular genetics · 2014Article
- Pharmacogenomics of cardiovascular complications in diabetes and obesity.Recent patents on biotechnology · 2014Review
- Applications of CYP450 testing in the clinical setting.Molecular diagnosis & therapy · 2013Review
- Antidepressants, metoprolol and the risk of bradycardia.Therapeutic advances in psychopharmacology · 2012Article
- Do CYP2D6 genotypes reflect oxycodone requirements for cancer patients treated for cancer pain? A cross-sectional multicentre study.European journal of clinical pharmacology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate individual metabolism-related determinants of metoprolol disposition and effects in patients receiving the drug as standard treatment for acute myocardial infarction (AMI).
methodsWe recruited 187 AMI patients receiving metoprolol on clinical grounds and genotyped them for CYP2D6 *3, *4, *10, and gene duplication. Heart rates (HR) at admission and discharge were registered. Clinical details were derived from the case histories. Metoprolol and alpha-hydroxy-metoprolol were analyzed by HPLC in plasma before and after 2, 6 and 12 h post dose in the first 115 patients. HR at rest was registered after each sampling. Ventricular rhythm disturbance (VRD) association with CYP2D6 activity, found accidentally, was studied in a newly formed subgroup (n = 23).
resultsMetoprolol represented 85% of all beta-blocker prescriptions. CYP2D6 genotype distribution was comparable with other Caucasian populations. Genotypically poor metabolizers (PM, n = 2) exhibited the most pronounced bradycardia at discharge, while in the ultrarapid metabolizers (UM, n = 7) therapeutic effect was not achieved. Metoprolol and alpha-hydroxy-metoprolol plasma concentration AUCs differed significantly between the genotypes corresponding to predicted metabolic activity (P < 0.005). Correspondingly, the mean HRs were lower in PMs and increased with increasing number of active CYP2D6 genes (P < 0.05). Trough metoprolol concentrations were only quantifiable in patients with at least one mutated allele. Neither decreased cardiac ejection fraction nor age and gender influenced metoprolol disposition. Higher mean number of active CYP2D6 genes was found in patients with VRDs (2.2 vs. 1.7), which could not be clearly explained by metoprolol concentrations. CYP2D6 gene duplication was overrepresented in this group (22 vs. 2%, P = 0.0002).
conclusionMetoprolol disposition and effects are mainly controlled by CYP2D6 genotype. Patients with gene duplication are at high risk of not benefiting from treatment due to lower metoprolol concentrations. Higher CYP2D6 activity seems to be associated with VRDs complicating AMI, being a negative prognostic factor for patients' survival.
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