PT  - JOURNAL ARTICLE
AU  - Lai, Yi-Chun
AU  - Kuo, Tzong-Fu
AU  - Chen, Chien-Kuang
AU  - Tsai, Han-Ju
AU  - Lee, Shoei-Sheng
TI  - Metabolism of Dicentrine: Identification of the Phase I and Phase II Metabolites in Miniature Pig Urine
AID  - 10.1124/dmd.110.033795
DP  - 2010 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 1714--1722
VI  - 38
IP  - 10
4099  - http://dmd.aspetjournals.org/content/38/10/1714.short
4100  - http://dmd.aspetjournals.org/content/38/10/1714.full
SO  - Drug Metab Dispos2010 Oct 01; 38
AB  - The metabolic profile of dicentrine, a selective α1-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-OCH2O-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.