Effect of concomitant use of yokukansan on steady‐state blood concentrations of donepezil and risperidone in real‐world clinical practice

Abstract Aim Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady‐state blood concentrations of donepezil, risperidone, and the major met...

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Main Authors: Junji Saruwatari, Tetsuya Kaneko, Tsukasa Murata, Haruka Narise, Sawa Kugimoto, Eri Nishimura, Natsuki Tetsuka, Misaki Ando, Momo Oi, Masako Ota, Nayumi Hamada, Keiichiro Kaneda, Shiro Furusho, Masakatsu Sakamoto, Ayami Kajiwara‐Morita, Kazutaka Oda, Kentaro Oniki, Keishi Ueda, Hirofumi Jono, Norio Yasui‐Furukori
Format: Article
Language:English
Published: Wiley 2024-09-01
Series:Neuropsychopharmacology Reports
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Online Access:https://doi.org/10.1002/npr2.12459
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author Junji Saruwatari
Tetsuya Kaneko
Tsukasa Murata
Haruka Narise
Sawa Kugimoto
Eri Nishimura
Natsuki Tetsuka
Misaki Ando
Momo Oi
Masako Ota
Nayumi Hamada
Keiichiro Kaneda
Shiro Furusho
Masakatsu Sakamoto
Ayami Kajiwara‐Morita
Kazutaka Oda
Kentaro Oniki
Keishi Ueda
Hirofumi Jono
Norio Yasui‐Furukori
author_facet Junji Saruwatari
Tetsuya Kaneko
Tsukasa Murata
Haruka Narise
Sawa Kugimoto
Eri Nishimura
Natsuki Tetsuka
Misaki Ando
Momo Oi
Masako Ota
Nayumi Hamada
Keiichiro Kaneda
Shiro Furusho
Masakatsu Sakamoto
Ayami Kajiwara‐Morita
Kazutaka Oda
Kentaro Oniki
Keishi Ueda
Hirofumi Jono
Norio Yasui‐Furukori
author_sort Junji Saruwatari
collection DOAJ
description Abstract Aim Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady‐state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real‐world clinical setting. Methods A non‐randomized, open‐label, single‐arm study examining drug–drug interactions was conducted. Fifteen dementia patients taking donepezil for at least 4 weeks and eight schizophrenia patients taking risperidone for at least 2 weeks were orally administered 2.5 g of yokukansan three times a day before or between meals, and blood samples were collected before and 8 weeks after starting co‐treatment with yokukansan. Plasma concentrations of donepezil, risperidone, and each metabolite were measured using high‐performance liquid chromatography–tandem mass spectrometry and compared before and after the 8‐week administration of yokukansan. Results The plasma concentrations of donepezil and its metabolites (6‐O‐desmethyl‐donepezil, 5‐O‐desmethyl‐donepezil, and donepezil‐N‐oxide), risperidone, and its metabolite paliperidone did not differ before and after the 8‐week treatment with yokukansan. Conclusions The findings of this study show that the concomitant use of yokukansan may have little clinical impact on the steady‐state blood levels of donepezil and risperidone in patients with dementia or schizophrenia.
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spelling doaj-art-386f5c7aa74645a3abe2bcb297fffb712024-11-08T11:46:40ZengWileyNeuropsychopharmacology Reports2574-173X2024-09-0144361461910.1002/npr2.12459Effect of concomitant use of yokukansan on steady‐state blood concentrations of donepezil and risperidone in real‐world clinical practiceJunji Saruwatari0Tetsuya Kaneko1Tsukasa Murata2Haruka Narise3Sawa Kugimoto4Eri Nishimura5Natsuki Tetsuka6Misaki Ando7Momo Oi8Masako Ota9Nayumi Hamada10Keiichiro Kaneda11Shiro Furusho12Masakatsu Sakamoto13Ayami Kajiwara‐Morita14Kazutaka Oda15Kentaro Oniki16Keishi Ueda17Hirofumi Jono18Norio Yasui‐Furukori19Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences Kumamoto University Kumamoto JapanDivision of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences Kumamoto University Kumamoto JapanKumamoto Seimei Hospital Kumamoto JapanDivision of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences Kumamoto University Kumamoto JapanDivision of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences Kumamoto University Kumamoto JapanDivision of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences Kumamoto University Kumamoto JapanDepartment of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences Kumamoto University Kumamoto JapanDepartment of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences Kumamoto University Kumamoto JapanDepartment of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences Kumamoto University Kumamoto JapanDepartment of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences Kumamoto University Kumamoto JapanKumamoto Seimei Hospital Kumamoto JapanKumamoto Seimei Hospital Kumamoto JapanKumamoto Seimei Hospital Kumamoto JapanKumamoto Seimei Hospital Kumamoto JapanDivision of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences Kumamoto University Kumamoto JapanDepartment of Pharmacy Kumamoto University Hospital Kumamoto JapanDivision of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences Kumamoto University Kumamoto JapanKumamoto Seimei Hospital Kumamoto JapanDepartment of Pharmacy Kumamoto University Hospital Kumamoto JapanDepartment of Psychiatry, School of Medicine Dokkyo Medical University Tochigi JapanAbstract Aim Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady‐state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real‐world clinical setting. Methods A non‐randomized, open‐label, single‐arm study examining drug–drug interactions was conducted. Fifteen dementia patients taking donepezil for at least 4 weeks and eight schizophrenia patients taking risperidone for at least 2 weeks were orally administered 2.5 g of yokukansan three times a day before or between meals, and blood samples were collected before and 8 weeks after starting co‐treatment with yokukansan. Plasma concentrations of donepezil, risperidone, and each metabolite were measured using high‐performance liquid chromatography–tandem mass spectrometry and compared before and after the 8‐week administration of yokukansan. Results The plasma concentrations of donepezil and its metabolites (6‐O‐desmethyl‐donepezil, 5‐O‐desmethyl‐donepezil, and donepezil‐N‐oxide), risperidone, and its metabolite paliperidone did not differ before and after the 8‐week treatment with yokukansan. Conclusions The findings of this study show that the concomitant use of yokukansan may have little clinical impact on the steady‐state blood levels of donepezil and risperidone in patients with dementia or schizophrenia.https://doi.org/10.1002/npr2.12459drug interactionsherb‐drug interactionsKampometabolismpharmacokinetics
spellingShingle Junji Saruwatari
Tetsuya Kaneko
Tsukasa Murata
Haruka Narise
Sawa Kugimoto
Eri Nishimura
Natsuki Tetsuka
Misaki Ando
Momo Oi
Masako Ota
Nayumi Hamada
Keiichiro Kaneda
Shiro Furusho
Masakatsu Sakamoto
Ayami Kajiwara‐Morita
Kazutaka Oda
Kentaro Oniki
Keishi Ueda
Hirofumi Jono
Norio Yasui‐Furukori
Effect of concomitant use of yokukansan on steady‐state blood concentrations of donepezil and risperidone in real‐world clinical practice
Neuropsychopharmacology Reports
drug interactions
herb‐drug interactions
Kampo
metabolism
pharmacokinetics
title Effect of concomitant use of yokukansan on steady‐state blood concentrations of donepezil and risperidone in real‐world clinical practice
title_full Effect of concomitant use of yokukansan on steady‐state blood concentrations of donepezil and risperidone in real‐world clinical practice
title_fullStr Effect of concomitant use of yokukansan on steady‐state blood concentrations of donepezil and risperidone in real‐world clinical practice
title_full_unstemmed Effect of concomitant use of yokukansan on steady‐state blood concentrations of donepezil and risperidone in real‐world clinical practice
title_short Effect of concomitant use of yokukansan on steady‐state blood concentrations of donepezil and risperidone in real‐world clinical practice
title_sort effect of concomitant use of yokukansan on steady state blood concentrations of donepezil and risperidone in real world clinical practice
topic drug interactions
herb‐drug interactions
Kampo
metabolism
pharmacokinetics
url https://doi.org/10.1002/npr2.12459
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