Trial reportBritish journal of clinical pharmacology2014
Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance.
Trial report in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Pooled it
- Donepezil plasma concentrations, CYP2D6 and CYP3A4 phenotypes, and cognitive outcome in Alzheimer's disease.European journal of clinical pharmacology · 2016Trial
- Therapeutic dosage assessment based on population pharmacokinetics of a novel single-dose transdermal donepezil patch in healthy volunteers.European journal of clinical pharmacology · 2015Trial
- Single dose pharmacokinetics of the novel transdermal donepezil patch in healthy volunteers.Drug design, development and therapy · 2015Trial
- Network dynamics-based subtyping of Alzheimer's disease with microglial genetic risk factors.Alzheimer's research & therapy · 2024Article
- Pharmacogenomics of Dementia: Personalizing the Treatment of Cognitive and Neuropsychiatric Symptoms.Genes · 2023Review
- An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Cholinesterase inhibitors-associated torsade de pointes/QT prolongation: a real-world pharmacovigilance study.Frontiers in pharmacology · 2023Article
- Pharmacogenetics of Donepezil and Memantine in Healthy Subjects.Journal of personalized medicine · 2022Article
- Personalized Management and Treatment of Alzheimer's Disease.Life (Basel, Switzerland) · 2022Review
- Neurobiological Highlights of Cognitive Impairment in Psychiatric Disorders.International journal of molecular sciences · 2022Review
- Pharmacogenomics of Alzheimer's Disease: Novel Strategies for Drug Utilization and Development.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Association between human paraoxonase 2 protein and efficacy of acetylcholinesterase inhibiting drugs used against Alzheimer's disease.PloS one · 2021Article
- Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review.Therapeutics and clinical risk management · 2021Review
- Pharmacogenomics, How to Deal with Different Types of Variants in Next Generation Sequencing Data in the Personalized Medicine Area.Journal of clinical medicine · 2020Review
- Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia.International journal of molecular sciences · 2020Review
- Effect of the Most Relevant CYP3A4 and CYP3A5 Polymorphisms on the Pharmacokinetic Parameters of 10 CYP3A Substrates.Biomedicines · 2020Article
- Gene Polymorphisms Affecting the Pharmacokinetics and Pharmacodynamics of Donepezil Efficacy.Frontiers in pharmacology · 2020Review
- Serum Concentrations of Cholinesterase Inhibitors in Patients With Alzheimer's Dementia Are Frequently Below the Recommended Levels.Frontiers in pharmacology · 2020Article
- Therapeutic Drug Monitoring of Rivastigmine and Donepezil Under Consideration of CYP2D6 Genotype-Dependent Metabolism of Donepezil.Drug design, development and therapy · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsA large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting.
methodsA population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1.
resultsThe average donepezil clearance was 7.3 l h(-1) with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers.
conclusionThe pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment.
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