Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease

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...

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Autores principales:	Yoshiyuki Kagawa, Yoshiaki Yamamoto, Ayami Ueno, Kengo Inomata, Mayu Tezuka, Takashi Osawa, Yasuharu Yazawa, Toshio Maeda, Tomokazu Obi
Formato:	article
Lenguaje:	EN
Publicado:	Karger Publishers 2021
Materias:	alzheimer’s disease behavioral and psychological symptoms of dementia donepezil pharmacokinetics polymorphism Neurology. Diseases of the nervous system RC346-429 Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/9092d961ecd94bbf8758a46b3d1fdcea
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spelling	oai:doaj.org-article:9092d961ecd94bbf8758a46b3d1fdcea2021-12-02T12:40:23ZImpact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease1664-546410.1159/000516938https://doaj.org/article/9092d961ecd94bbf8758a46b3d1fdcea2021-12-01T00:00:00Zhttps://www.karger.com/Article/FullText/516938https://doaj.org/toc/1664-5464Background/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.Yoshiyuki KagawaYoshiaki YamamotoAyami UenoKengo InomataMayu TezukaTakashi OsawaYasuharu YazawaToshio MaedaTomokazu ObiKarger Publishersarticlealzheimer’s diseasebehavioral and psychological symptoms of dementiadonepezilpharmacokineticspolymorphismNeurology. Diseases of the nervous systemRC346-429GeriatricsRC952-954.6ENDementia and Geriatric Cognitive Disorders Extra, Vol 11, Iss 3, Pp 264-272 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	alzheimer’s disease behavioral and psychological symptoms of dementia donepezil pharmacokinetics polymorphism Neurology. Diseases of the nervous system RC346-429 Geriatrics RC952-954.6
spellingShingle	alzheimer’s disease behavioral and psychological symptoms of dementia donepezil pharmacokinetics polymorphism Neurology. Diseases of the nervous system RC346-429 Geriatrics RC952-954.6 Yoshiyuki Kagawa Yoshiaki Yamamoto Ayami Ueno Kengo Inomata Mayu Tezuka Takashi Osawa Yasuharu Yazawa Toshio Maeda Tomokazu Obi Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease
description	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.
format	article
author	Yoshiyuki Kagawa Yoshiaki Yamamoto Ayami Ueno Kengo Inomata Mayu Tezuka Takashi Osawa Yasuharu Yazawa Toshio Maeda Tomokazu Obi
author_facet	Yoshiyuki Kagawa Yoshiaki Yamamoto Ayami Ueno Kengo Inomata Mayu Tezuka Takashi Osawa Yasuharu Yazawa Toshio Maeda Tomokazu Obi
author_sort	Yoshiyuki Kagawa
title	Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease
title_short	Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease
title_full	Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease
title_fullStr	Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease
title_full_unstemmed	Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease
title_sort	impact of plasma donepezil concentration on behavioral and psychological symptoms of dementia in patients with alzheimer’s disease
publisher	Karger Publishers
publishDate	2021
url	https://doaj.org/article/9092d961ecd94bbf8758a46b3d1fdcea
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Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease

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