Trial reportEuropean journal of clinical pharmacology2016
Genotype and co-medication dependent CYP2D6 metabolic activity: effects on serum concentrations of aripiprazole, haloperidol, risperidone, paliperidone and zuclopenthixol.
Trial report in European journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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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
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of probability estimates of worldwide variation of CYP2D6 and CYP2C19.Translational psychiatry · 2021Pooled it
- Trial
- Influence of CYP2D6 Genotypes and Phenotypes on the Plasma Levels and Clinical Response to Aripiprazole.Schizophrenia bulletin · 2026Article
- UHPLC-MS/MS for Antipsychotic Drug Monitoring: A Systematic Review of Clinical and Analytical Performance.Journal of clinical medicine · 2025Review
- Influence of CYP2D6 phenotype on adherence, adverse effects, and attitudes in aripiprazole and risperidone users.Acta neuropsychiatrica · 2025Article
- Effect of CYP2D6 pharmacogenetic phenotype and phenoconversion on serum concentrations of antidepressants and antipsychotics: a retrospective cohort study.International journal of clinical pharmacy · 2023Article
- Pharmacogenetics in the Treatment of Huntington's Disease: Review and Future Perspectives.Journal of personalized medicine · 2023Review
- Pharmacogenomics and non-genetic factors affecting drug response in autism spectrum disorder in Thai and other populations: current evidence and future implications.Frontiers in pharmacology · 2023Review
- CYP2D6 pharmacogenetics and phenoconversion in personalized medicine.Expert opinion on drug metabolism & toxicology · 2022Review
- Review: Influence of the CYP450 Genetic Variation on the Treatment of Psychotic Disorders.Journal of clinical medicine · 2021Review
- Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics.Pharmaceutics · 2021Review
- Resolving discordantPharmacogenomics · 2021Article
- Impact of age and CYP2D6 genotype on exposure of zuclopenthixol in patients using long-acting injectable versus oral formulation-an observational study including 2044 patients.European journal of clinical pharmacology · 2021Observational
- CYP2D6 in the Brain: Potential Impact on Adverse Drug Reactions in the Central Nervous System-Results From the ADRED Study.Frontiers in pharmacology · 2021Article
- Application of a Pharmacogenetics-Based Precision Medicine Model (5SPM) to Psychotic Patients That Presented Poor Response to Neuroleptic Therapy.Journal of personalized medicine · 2020Article
- Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review.Journal of clinical medicine · 2020Review
- Phenoconversion of CYP2D6 by inhibitors modifies aripiprazole exposure.European archives of psychiatry and clinical neuroscience · 2020Article
- Identification of a de novo FOXP1 mutation and incidental discovery of inherited genetic variants contributing to a case of autism spectrum disorder and epilepsy.Molecular genetics & genomic medicine · 2019Article
- Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment.Nature communications · 2018Article
- Precision medicine: does ethnicity information complement genotype-based prescribing decisions?Therapeutic advances in drug safety · 2018Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTherapeutic drug monitoring (TDM) of antipsychotics can aid in therapy optimization, explaining adverse effects or non-response. One reason for therapeutic failure or adverse effects is caused by genetic variations in the cytochrome P450 drug-metabolizing genes. The aim of this study was to evaluate the impact of CYP2D6 polymorphisms on steady-state serum concentrations of antipsychotics metabolized by CYP2D6, taking into account the co-medication with CYP2D6 inhibitors.
methodsSerum and EDTA samples were collected from 82 psychiatric patients. After a liquid-liquid extraction, serum samples were analyzed using an ultra-high performance liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS) method for quantification of the antipsychotics. CYP2D6 genotyping was performed using the Luminex xTAG® CYP2D6 Kit v3 (Luminex Corporation). Patients were divided into five phenotype subgroups by calculation of the activity score (AS): poor metabolizers (PM; AS 0), intermediate metabolizers (IM; AS 0.5-1), extensive metabolizers with slow activity (EM-s; AS 1-1.5), extensive metabolizers with fast activity (EM-f; AS 2), and ultra-rapid metabolizers (UM; AS >2). The influence of the phenotypes on the concentration-to-dose and metabolite-to-parent ratios was evaluated.
resultsOverall, 6.1 % UM (n = 5), 25.6 % EM-f (n = 21), 46.3 % EM-s (n = 38), 1.2 % EM-s/EM-f (n = 1), 6.1 % IM (n = 5), and 14.6 % PM (n = 12) were found, taking co-administration of strong and moderate CYP2D6 inhibitors into account (phenoconversion). It was demonstrated that CYP2D6 polymorphisms affect the serum concentrations of aripiprazole (n = 18), haloperidol (n = 11), risperidone (n = 20), and zuclopenthixol (n = 6), while no influence was seen on the paliperidone serum concentrations (n = 31).
conclusionsEven with a small number of patients per antipsychotic, the importance of CYP2D6 genotyping was still clearly stated. This study illustrates the high potential of combining TDM and CYP2D6 genotyping in clinical practice.
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Registered trials
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