Hsu_1990_Drug.Metab.Dispos_18_779

Reference

Title : Identification of the urinary metabolites of tacrine in the rat - Hsu_1990_Drug.Metab.Dispos_18_779
Author(s) : Hsu RS , Shutske GM , DiLeo EM , Chesson SM , Linville AR , Allen RC
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 18 :779 , 1990
Abstract :

Tacrine (THA) is a potent cholinesterase inhibitor being studied for the treatment of Alzheimer's disease. The metabolism and excretion of THA were studied in rats following a single oral dose of 20 mg/kg of THA. The results show THA was extensively metabolized in rats after oral administration. Three major urinary metabolites were isolated by HPLC on a semi-prep analytical phenyl column, and subsequent purification of the individual fractions on a semi-prep analytical cyano column. The major metabolic pathways involve the hydroxylation of the saturated ring at positions 1, 2, and 4. The structures of the metabolites 9-amino-1,2,3,4-tetrahydroacridin-1-ol (1-OH-THA), 9-amino-1,2,3,4-tetrahydroacridin-2-ol (2-OH-THA), and 9-amino-1,2,3,4-tetrahydroacridin-4-ol (4-OH-THA) were determined by electron impact mass spectrometry and/or 1H-NMR, and compared with synthetic references. The urinary excretion of THA and metabolites was quantitated by HPLC with UV detection. About 60% of the oral dose was eliminated as total THA, 1-OH-THA, 2-OH-THA, and 4-OH-THA over a 48-hr collection interval; and the non-conjugated THA and hydroxylated metabolites accounted for 45% of the dose.

PubMedSearch : Hsu_1990_Drug.Metab.Dispos_18_779
PubMedID: 1981736

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Citations formats

Hsu RS, Shutske GM, DiLeo EM, Chesson SM, Linville AR, Allen RC (1990)
Identification of the urinary metabolites of tacrine in the rat
Drug Metabolism & Disposition: The Biological Fate of Chemicals 18 :779

Hsu RS, Shutske GM, DiLeo EM, Chesson SM, Linville AR, Allen RC (1990)
Drug Metabolism & Disposition: The Biological Fate of Chemicals 18 :779