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

Abstract

BackgroundThe 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.