{"title":"Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer's Disease.","authors":"Yoshiyuki Kagawa, Yoshiaki Yamamoto, Ayami Ueno, Kengo Inomata, Mayu Tezuka, Takashi Osawa, Yasuharu Yazawa, Toshio Maeda, Tomokazu Obi","doi":"10.1159/000516938","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aims: </strong>The behavioral and psychological symptoms of dementia (BPSD) detract from the quality of life of not only dementia patients but also their family members and caregivers. Donepezil is used to treat Alzheimer's disease and is metabolized via cytochrome P450 (CYP) 2D6 and CYP3A4/5. It is controversial whether donepezil improves or exacerbates BPSD. This study investigated the relationships among BPSD, the pharmacokinetics of donepezil including its metabolite, 6-O-desmethyl donepezil, genetic polymorphisms of CYPs and P-glycoprotein, and patient backgrounds in 52 patients with Alzheimer's disease.</p><p><strong>Methods: </strong>BPSD were assessed using the Neuropsychiatric Inventory (NPI), with scores ≥20 points defined as severe BPSD. Plasma donepezil and 6-O-desmethyl donepezil concentrations were measured using liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>Although significant relationships between NPI scores and plasma donepezil concentrations were not seen, none of the 15 patients (29%) with high plasma donepezil concentrations (≥60 ng/mL) developed severe BPSD. Polymorphisms of <i>CYP2D6</i>, <i>CYP3A5</i>, and <i>ABCB1</i> did not influence NPI scores. There were no significant relationships between NPI and patient background factors such as dosing regimen, concomitant use of other drugs, or laboratory test results. Two patients who underwent multiple blood samplings over 2 years showed an inverse correlation between plasma donepezil concentrations and NPI scores.</p><p><strong>Discussion/conclusions: </strong>These results indicate that higher plasma concentrations of donepezil contribute to preventing or alleviating rather than developing or deteriorating BPSD.</p>","PeriodicalId":38017,"journal":{"name":"Dementia and Geriatric Cognitive Disorders Extra","volume":"11 3","pages":"264-272"},"PeriodicalIF":1.4000,"publicationDate":"2021-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8a/8f/dee-0011-0264.PMC8739384.pdf","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Dementia and Geriatric Cognitive Disorders Extra","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1159/000516938","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/9/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 1
Abstract
Background/aims: The behavioral and psychological symptoms of dementia (BPSD) detract from the quality of life of not only dementia patients but also their family members and caregivers. Donepezil is used to treat Alzheimer's disease and is metabolized via cytochrome P450 (CYP) 2D6 and CYP3A4/5. It is controversial whether donepezil improves or exacerbates BPSD. This study investigated the relationships among BPSD, the pharmacokinetics of donepezil including its metabolite, 6-O-desmethyl donepezil, genetic polymorphisms of CYPs and P-glycoprotein, and patient backgrounds in 52 patients with Alzheimer's disease.
Methods: BPSD were assessed using the Neuropsychiatric Inventory (NPI), with scores ≥20 points defined as severe BPSD. Plasma donepezil and 6-O-desmethyl donepezil concentrations were measured using liquid chromatography-tandem mass spectrometry.
Results: Although significant relationships between NPI scores and plasma donepezil concentrations were not seen, none of the 15 patients (29%) with high plasma donepezil concentrations (≥60 ng/mL) developed severe BPSD. Polymorphisms of CYP2D6, CYP3A5, and ABCB1 did not influence NPI scores. There were no significant relationships between NPI and patient background factors such as dosing regimen, concomitant use of other drugs, or laboratory test results. Two patients who underwent multiple blood samplings over 2 years showed an inverse correlation between plasma donepezil concentrations and NPI scores.
Discussion/conclusions: These results indicate that higher plasma concentrations of donepezil contribute to preventing or alleviating rather than developing or deteriorating BPSD.
背景/目的:痴呆症(BPSD)的行为和心理症状不仅影响痴呆症患者的生活质量，而且影响其家庭成员和照顾者的生活质量。多奈哌齐用于治疗阿尔茨海默病，通过细胞色素P450 (CYP) 2D6和CYP3A4/5代谢。多奈哌齐是改善还是加重BPSD仍有争议。本研究对52例阿尔茨海默病患者的BPSD、多奈哌齐及其代谢物6- o -去甲基多奈哌齐的药代动力学、CYPs和p -糖蛋白遗传多态性以及患者背景进行了研究。方法:采用神经精神量表(NPI)对BPSD进行评估，评分≥20分定义为重度BPSD。采用液相色谱-串联质谱法测定血浆多奈哌齐和6- o -去甲基多奈哌齐浓度。结果:虽然NPI评分与血浆多奈哌齐浓度之间没有明显的关系，但15例血浆多奈哌齐浓度高(≥60 ng/mL)的患者(29%)中没有发生严重的BPSD。CYP2D6、CYP3A5和ABCB1的多态性对NPI评分没有影响。NPI与患者背景因素(如给药方案、同时使用其他药物或实验室检查结果)之间没有显著关系。2例患者在2年内多次采血，血浆多奈哌齐浓度与NPI评分呈负相关。讨论/结论:这些结果表明，较高血浆浓度的多奈哌齐有助于预防或减轻BPSD，而不是发展或恶化BPSD。
期刊介绍：
This open access and online-only journal publishes original articles covering the entire spectrum of cognitive dysfunction such as Alzheimer’s and Parkinson’s disease, Huntington’s chorea and other neurodegenerative diseases. The journal draws from diverse related research disciplines such as psychogeriatrics, neuropsychology, clinical neurology, morphology, physiology, genetic molecular biology, pathology, biochemistry, immunology, pharmacology and pharmaceutics. Strong emphasis is placed on the publication of research findings from animal studies which are complemented by clinical and therapeutic experience to give an overall appreciation of the field. Dementia and Geriatric Cognitive Disorders Extra provides additional contents based on reviewed and accepted submissions to the main journal Dementia and Geriatric Cognitive Disorders Extra .
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