{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T03:33:11Z","timestamp":1747193591629,"version":"3.40.5"},"reference-count":31,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dement Geriatr Cogn Disord Extra"],"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background\/Aims:&lt;\/i&gt;&lt;\/b&gt; 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\u2019s 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\u2019s disease. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; BPSD were assessed using the Neuropsychiatric Inventory (NPI), with scores \u226520 points defined as severe BPSD. Plasma donepezil and 6-O-desmethyl donepezil concentrations were measured using liquid chromatography\u2013tandem mass spectrometry. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Although significant relationships between NPI scores and plasma donepezil concentrations were not seen, none of the 15 patients (29%) with high plasma donepezil concentrations (\u226560 ng\/mL) developed severe BPSD. Polymorphisms of &lt;i&gt;CYP2D6&lt;\/i&gt;, &lt;i&gt;CYP3A5&lt;\/i&gt;, and &lt;i&gt;ABCB1&lt;\/i&gt; 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. &lt;b&gt;&lt;i&gt;Discussion\/Conclusions:&lt;\/i&gt;&lt;\/b&gt; These results indicate that higher plasma concentrations of donepezil contribute to preventing or alleviating rather than developing or deteriorating BPSD. <\/jats:p>","DOI":"10.1159\/000516938","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T22:00:58Z","timestamp":1638482458000},"page":"264-272","source":"Crossref","is-referenced-by-count":3,"title":["Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer\u2019s Disease"],"prefix":"10.1159","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4902-1625","authenticated-orcid":false,"given":"Yoshiyuki","family":"Kagawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayami","family":"Ueno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kengo","family":"Inomata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayu","family":"Tezuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Osawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuharu","family":"Yazawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshio","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomokazu","family":"Obi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13439"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610216000922"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.4236\/aad.2013.21005"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-10-87"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x14666151208114232"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2010.02.013"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160418"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S99032"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1177\/1756285617712979"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/s0167-4943(01)00187-x"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-200211000-00007"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S37688"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1159\/000362871"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1177\/2045125313508130"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1345\/aph.17150"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-016-2033-1"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-010-0883-5"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0b013e318255a8f9"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-003-0594-2"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.48.5_suppl_6.10s"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-011-0618-0"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-86-6-827"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.1552"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.1095"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1600991"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12325"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2001.117412"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-017-3506-3"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.2147\/PGPM.S211259"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.066654"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2019.e02662"}],"container-title":["Dementia 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