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The measured CSF/plasma donepezil concentration ratio but not individually measured CSF and plasma concentrations significantly increase over 24 h after donepezil treatment in patients with Alzheimer's disease

M. Valis, A. Dlabkova, J. Hort, F. Angelucci, J. Pejchal, K. Kuca, Z. Pavelek, JZ. Karasova, M. Novotny

. 2023 ; 159 (-) : 114223. [pub] 20230109

Language English Country France

Document type Randomized Controlled Trial, Journal Article

Persistent link   https://www.medvik.cz/link/bmc23003977

BACKGROUND: The acetylcholinesterase inhibitor donepezil is administered as a treatment for Alzheimer's disease (AD). However, the appropriate donepezil dosage is still a matter of debate. METHODS: Forty AD patients receiving 10 mg/day of donepezil were randomly divided into four groups based on the time of plasma and cerebrospinal fluid (CSF) sampling: 6 h (n = 5), 12 h (n = 12), 18 h (n = 6) and 24 h (n = 17) after donepezil administration. High-performance liquid chromatography measured the donepezil concentration in plasma samples and CSF samples collected at 4-time points. RESULTS: Plasma and CSF levels among the groups were not significantly different. Conversely, the CSF/plasma donepezil concentration ratio considerably increased in the 24 h group compared to the 6 h (p < 0.005) and 12 h (p < 0.05) groups. CONCLUSION: The measurement of the CSF/plasma donepezil concentration ratio could be used to better evaluate the optimal dose of donepezil.

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$a Valis, Martin $u Department of Neurology, Faculty of Medicine and University Hospital Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic. Electronic address: martin.valis@fnhk.cz
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$a The measured CSF/plasma donepezil concentration ratio but not individually measured CSF and plasma concentrations significantly increase over 24 h after donepezil treatment in patients with Alzheimer's disease / $c M. Valis, A. Dlabkova, J. Hort, F. Angelucci, J. Pejchal, K. Kuca, Z. Pavelek, JZ. Karasova, M. Novotny
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$a BACKGROUND: The acetylcholinesterase inhibitor donepezil is administered as a treatment for Alzheimer's disease (AD). However, the appropriate donepezil dosage is still a matter of debate. METHODS: Forty AD patients receiving 10 mg/day of donepezil were randomly divided into four groups based on the time of plasma and cerebrospinal fluid (CSF) sampling: 6 h (n = 5), 12 h (n = 12), 18 h (n = 6) and 24 h (n = 17) after donepezil administration. High-performance liquid chromatography measured the donepezil concentration in plasma samples and CSF samples collected at 4-time points. RESULTS: Plasma and CSF levels among the groups were not significantly different. Conversely, the CSF/plasma donepezil concentration ratio considerably increased in the 24 h group compared to the 6 h (p < 0.005) and 12 h (p < 0.05) groups. CONCLUSION: The measurement of the CSF/plasma donepezil concentration ratio could be used to better evaluate the optimal dose of donepezil.
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$a Dlabkova, Alzbeta $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, the University of Defense in Brno, Hradec Kralove, Czech Republic. Electronic address: alzbeta.dlabkova@unob.cz
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$a Hort, Jakub $u Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic. Electronic address: jakub.hort@gmail.com
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$a Angelucci, Francesco $u Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic
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$a Pejchal, Jaroslav $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, the University of Defense in Brno, Hradec Kralove, Czech Republic
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$a Kuca, Kamil $u Department of Neurology, Faculty of Medicine and University Hospital Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic; Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic. Electronic address: kamil.kuca@fnhk.cz
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$a Pavelek, Zbysek $u Department of Neurology, Faculty of Medicine and University Hospital Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
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$a Karasova, Jana Zdarova $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, the University of Defense in Brno, Hradec Kralove, Czech Republic; Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic
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$a Novotny, Michal $u Department of Neurology, Faculty of Medicine and University Hospital Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic. Electronic address: m.novas82@gmail.com
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