Metabolism of dicentrine: identification of the phase I and phase II metabolites in miniature pig urine

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Yi-Chun LaiShoei-Sheng Lee

Abstract

The metabolic profile of dicentrine, a selective α(1)-adrenoceptor antagonist with potent antiarrhythmic and antihypertensive activities, in miniature pig urine via oral administration was investigated for the first time. The urine, collected after a single oral administration of dicentrine, was pretreated using solvent extraction and column chromatographic methods to identify the metabolites containing fractions. Twenty-four metabolites (MI-1-9 and MII-1-15), of which 21 compounds are new, were identified by mass spectrometry and high-performance liquid chromatography-diode array detector solid-phase extraction-NMR techniques. Of these, 14 metabolites (MI-5, MII-1 and 2, and MII-5-15) were further isolated for structure confirmation. The phase I metabolic transformations of dicentrine were found to be N-demethylation, N-oxidation, O-demethylation (9,10-OMe), O,O-demethylenation (1-OCH(2)O-2), and hydroxylation at the benzylic (C-4) and the aromatic (C-3) positions, whereas those for the phase II were O-glucuronidation and O-glucosylation of the phenolic group of the phase I metabolites.

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Citations

Dec 30, 2014·Journal of Pharmacological and Toxicological Methods·Lars Dalgaard
May 2, 2015·Journal of Pharmaceutical and Biomedical Analysis·Yung-Ping LeeShoei-Sheng Lee
May 23, 2016·European Journal of Drug Metabolism and Pharmacokinetics·Baojuan XueShuangcheng Ma
Mar 8, 2017·Drug Metabolism Reviews·Guangyi YangMing Hu
May 17, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yung-Ping LeeShoei-Sheng Lee
Apr 28, 2020·Phytochemistry Reviews : Proceedings of the Phytochemical Society of Europe·Yueping JiangShao Liu
Feb 15, 2011·Journal of Natural Products·Chien-Kuang ChenShoei-Sheng Lee

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