RT Journal Article
SR Electronic
T1 Metabolism of Dicentrine: Identification of the Phase I and Phase II Metabolites in Miniature Pig Urine
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1714
OP 1722
DO 10.1124/dmd.110.033795
VO 38
IS 10
A1 Yi-Chun Lai
A1 Tzong-Fu Kuo
A1 Chien-Kuang Chen
A1 Han-Ju Tsai
A1 Shoei-Sheng Lee
YR 2010
UL http://dmd.aspetjournals.org/content/38/10/1714.abstract
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.