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• W2164352431 abstract "Donepezil hydrochloride (Aricept) is a drug for the treatment of Alzheimer's disease. The absorption, distribution, metabolism, and excretion of donepezil were investigated in male Sprague-Dawley rats after a single oral administration. Orally administered (14)C-labeled donepezil was absorbed rapidly. The plasma level of unchanged donepezil declined more rapidly than that of radioactivity, and the brain level of radioactivity declined almost in parallel with the plasma level of unchanged donepezil. The ratio of donepezil to total radioactivity in brain was 86.9 to 93.0%, indicating low permeability of the metabolites through the blood-brain barrier. No heterogeneous localization of radioactivity was recognized in the brain and the concentration in each part of the brain was 1.74 to 2.24 times the plasma concentration. Cumulative biliary, urinary, and fecal excretion of radioactivity in bile duct-cannulated rats was 72.9, 24.4, and 8.84%, respectively, of the administered radioactivity at 48 h after administration. These results indicate that the absorption of donepezil is almost complete, and that its metabolites are mainly excreted into feces through the bile and some of them are subject to enterohepatic circulation. The metabolism of donepezil was extensive in rats and involved O-demethylation, aromatic hydroxylation, N-dealkylation, N-oxidation, and glucuronide conjugation of O-demethylate. The structures of the metabolites were determined by mass spectrometry and (1)H-NMR analysis. In plasma, urine, and bile, O-glucuronides accounted for the majority of the radioactivity, and in brain, unchanged donepezil was mostly detected. No metabolites were found in brain. There was no notable accumulation of radioactivity in whole blood and tissues." @default.
• W2164352431 created "2016-06-24" @default.
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• W2164352431 date "1999-12-01" @default.
• W2164352431 modified "2023-09-23" @default.
• W2164352431 title "Absorption, distribution, metabolism, and excretion of donepezil (Aricept) after a single oral administration to Rat." @default.
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• W2164352431 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10570021" @default.
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