These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Studies of metabolic pathways of trimebutine by simultaneous administration of trimebutine and its deuterium-labeled metabolite.
    Author: Miura Y, Chishima S, Takeyama S.
    Journal: Drug Metab Dispos; 1989; 17(4):455-62. PubMed ID: 2571489.
    Abstract:
    Trimebutine maleate (I), (+-)-2-dimethylamino-2-phenylbutyl 3,4,5-trimethoxybenzoate hydrogen maleate, and a deuterium-labeled sample of its hydrolyzed metabolite, 2-dimethylamino-2-phenylbutanol-d3 (II-d3), were simultaneously administered to experimental animals at an oral dose of 10 or 50 mumol/kg, and distribution ratios of the two alternative initial metabolic steps, i.e., ester hydrolysis and N-demethylation, were estimated by determining the composition of the urinary alcohol-moiety metabolites, II, and its mono- and di-demethylated metabolites, III and IV, by GC/MS. In dogs, the order of quantities of the metabolites from II-d3 was II much greater than III much greater than IV, showing predominance of conjugation over N-demethylation. However, this order was reversed when the amounts of the metabolites from I were compared, indicating that I was preferentially metabolized by N-demethylation followed by ester hydrolysis and conjugation in this order. In rats, a considerable proportion of I was presumed to be metabolized by ester hydrolysis before N-demethylation. In in vitro experiments employing the liver microsomes and homogenates of liver and small intestine from rats and dogs, it was found that both ester-hydrolizing and N-demethylating activities were higher in rats than in dogs, and the conjugating activity was higher in dogs than in rats. It was also found that I, having a high lipophilicity, was more susceptible to N-demethylation than less lipophilic II. These results from the in vitro experiments could account for the species differences in the distribution ratio of the metabolic pathways of I in vivo.
    [Abstract] [Full Text] [Related] [New Search]