ArticleEuropean journal of clinical pharmacology2006
Impact of the CYP2D6 polymorphism on steady-state plasma concentrations and clinical outcome of donepezil in Alzheimer's disease patients.
Article in European journal of clinical pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 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.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- The role of genetic polymorphisms on drug response in Alzheimer's disease: a systematic review.BMC medical genomics · 2025Pooled it
- Donepezil for cancer-related cognitive impairment: systematic review and meta-analysis.Clinical and experimental medicine · 2025Pooled it
- Donepezil plasma concentrations, CYP2D6 and CYP3A4 phenotypes, and cognitive outcome in Alzheimer's disease.European journal of clinical pharmacology · 2016Trial
- Characterization of hepatic enzyme activity in older adults with dementia: potential impact on personalizing pharmacotherapy.Clinical interventions in aging · 2015Trial
- Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance.British journal of clinical pharmacology · 2014Trial
- Trial
- The impact of CYP2D6 on donepezil concentration and its lack of effect on the treatment response and adverse effect in Korean patients with Alzheimer's disease.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Pharmacogenomics of Dementia: Personalizing the Treatment of Cognitive and Neuropsychiatric Symptoms.Genes · 2023Review
- Copy number variations of cytochromeAsian biomedicine : research, reviews and news · 2023Article
- Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review.Therapeutics and clinical risk management · 2021Review
- Cytochrome P450 (CYP450) Interactions Involving Atypical Antipsychotics are Common in Community-Dwelling Older Adults Treated for Behavioral and Psychological Symptoms of Dementia.Pharmacy (Basel, Switzerland) · 2020Article
- CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia.Pharmacogenomics and personalized medicine · 2020Article
- Therapeutic Drug Monitoring of Rivastigmine and Donepezil Under Consideration of CYP2D6 Genotype-Dependent Metabolism of Donepezil.Drug design, development and therapy · 2020Article
- Serum Concentrations of Cholinesterase Inhibitors in Patients With Alzheimer's Dementia Are Frequently Below the Recommended Levels.Frontiers in pharmacology · 2020Article
- Recent Developments in Metal-Based Drugs and Chelating Agents for Neurodegenerative Diseases Treatments.International journal of molecular sciences · 2019Review
- Influence ofPharmacogenomics and personalized medicine · 2019Article
- Effect of genetic polymorphisms on Alzheimer's disease treatment outcomes: an update.Clinical interventions in aging · 2019Review
- The Effect of Choline Acetyltransferase Genotype on Donepezil Treatment Response in Patients with Alzheimer's Disease.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2015Article
- Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect.Neuropsychiatric disease and treatment · 2014Review
- Pharmacodynamic, pharmacokinetic and pharmacogenetic aspects of drugs used in the treatment of Alzheimer's disease.Clinical pharmacokinetics · 2013Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe aims of this study were to evaluate the impact of the CYP2D6 polymorphism on both the steady-state plasma concentrations (Cp) and the clinical outcome of donepezil, a selective acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease (AD).
methodsForty-two patients of Caucasian ethnicity affected by probable AD were included in the study. All had been receiving therapy with donepezil for at least 3 months: 31 patients with 5 mg/day and 11 patients with 10 mg/day. The CYP2D6 genotype was analysed, and donepezil Cp was measured by using high-performance liquid chromatography.
resultsOn the basis of their CYP2D6 genotype, 30 patients could be classified as homozygous extensive metabolizers (EM), 10 as heterozygous EM and 2 as ultrarapid metabolizers (UM). No poor metabolizer was found. The dose and body weight-corrected median donepezil Cp were slightly, though not significantly, lower in homozygous than in heterozygous EM (0.33 vs. 0.41 ng/ml/mg/kg, respectively). The latter group consistently showed a better clinical response to treatment, as measured by change in Mini-Mental State Examination score (median: 1.40 vs. -1.30, respectively). UM patients had lower Cp than EM patients and showed no clinical improvement.
conclusionsOur preliminary data suggest that the CYP2D6 polymorphism influences both donepezil metabolism and therapeutic outcome and that a knowledge of a patient's CYP2D6 genotype together with donepezil concentration measurements might be useful in the context of improving the clinical efficacy of donepezil therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.