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Titolo:
Absorption, distribution, metabolism, and excretion of donepezil (ARICEPT)after a single oral administration to rat
Autore:
Matsui, K; Mishima, M; Nagai, Y; Yuzuriha, T; Yoshimura, T;
Indirizzi:
Eisai & Co Ltd, Drug Dynam Res Sect, Drug Safety & Disposit Res Labs, Tsukuba, Ibaraki 3002635, Japan Eisai & Co Ltd Tsukuba Ibaraki Japan 3002635 kuba, Ibaraki 3002635, Japan
Titolo Testata:
DRUG METABOLISM AND DISPOSITION
fascicolo: 12, volume: 27, anno: 1999,
pagine: 1406 - 1414
SICI:
0090-9556(199912)27:12<1406:ADMAEO>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENTEROHEPATIC CIRCULATION; LIVER-MICROSOMES; IDENTIFICATION; DISPOSITION; GLUCURONIDE; ACID; RECIRCULATION; INHIBITOR; DISEASE; RABBIT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Matsui, K Eisai & Co Ltd, Drug Dynam Res Sect, Drug Safety & Disposit Res Labs, 1-3 Tokodai 5-Chome, Tsukuba, Ibaraki 3002635, Japan Eisai & Co Ltd 1-3 Tokodai 5-Chome Tsukuba Ibaraki Japan 3002635
Citazione:
K. Matsui et al., "Absorption, distribution, metabolism, and excretion of donepezil (ARICEPT)after a single oral administration to rat", DRUG META D, 27(12), 1999, pp. 1406-1414

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 C-14-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 H-1-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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/01/20 alle ore 01:38:51