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Normal serum cholinesterase does not exclude donepezil or galantamine toxicity: an interpretive pitfall of
Taku Mayahara1, Tomohiro Katayama1, Kazuyoshi Matsuura1
1Department of Emergency and General Medicine, Kobe Ekisaikai Hospital, 1-21-1 Manabigaoka, Tarumi-ku, Kobe, Hyogo 655-0004, Japan.
None:
Routine "serum cholinesterase" testing primarily reflects butyrylcholinesterase (BuChE) activity and may not exclude toxicity from relatively acetylcholinesterase (AChE)-selective agents such as donepezil and galantamine. We conducted a targeted PubMed/MEDLINE search through December 2025 and identified published reports with documented cholinesterase measurements in clinically significant toxicity. Across these cases, serum BuChE and/or erythrocyte AChE activity was reported within the stated reference range despite symptomatic overdose. Potential explanations include limited BuChE inhibition by these agents and assay-related underestimation of reversible AChE inhibition under dilutional conditions. Normal serum cholinesterase should therefore not be used to rule out donepezil or galantamine toxicity; clearer test labeling as BuChE activity may reduce misinterpretation.
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