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.
Dement Geriatr Cogn Disord Extra 2021;11:264–272

中文翻译：

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血浆多奈哌齐浓度对阿尔茨海默病患者痴呆行为和心理症状的影响

背景/目的：痴呆症的行为和心理症状 (BPSD) 不仅会降低痴呆症患者的生活质量，还会影响其家庭成员和护理人员的生活质量。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 存在争议。本研究调查了 52 名阿尔茨海默病患者的 BPSD、多奈哌齐的药代动力学（包括其代谢物）、6-O-去甲基多奈哌齐、CYP 和 P-糖蛋白的遗传多态性以及患者背景之间的关系。方法：BPSD 使用神经精神量表 (NPI) 进行评估，分数≥20 分定义为严重 BPSD。使用液相色谱-串联质谱法测量血浆多奈哌齐和 6-O-去甲基多奈哌齐浓度。结果：尽管未发现 NPI 评分与血浆多奈哌齐浓度之间存在显着相关性，但 15 名血浆多奈哌齐浓度高（≥60 ng/mL）的患者（29%）均未出现严重的 BPSD。CYP2D6、CYP3A5和ABCB1的多态性不影响 NPI 分数。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）之间没有显着关系。两名在 2 年内接受多次血液采样的患者显示血浆多奈哌齐浓度与 NPI 评分之间存在负相关。讨论/结论：这些结果表明，较高的多奈哌齐血浆浓度有助于预防或减轻而不是发展或恶化 BPSD。
Dement Geriatr Cogn Disord Extra 2021;11:264–272