title: Metabolism of dicentrine: identification of the phase I and phase II metabolites in miniature pig urine.
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.
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, 1 Sec. 1 Jen-Ai Rd., Taipei, Taiwan, R.O.C.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Lai
authors.forename: Tzong-Fu
authors.initials: TF
authors.lastname: Kuo
authors.forename: Chien-Kuang
authors.initials: CK
authors.lastname: Chen
authors.forename: Han-Ju
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Shoei-Sheng
authors.initials: SS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001060:Aporphines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005260:Female; D020719:Glucuronides / Q000378:metabolism; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D008745:Methylation; D013552:Swine; D013556:Swine, Miniature; D053719:Tandem Mass Spectrometry
chemical_list: D001060:Aporphines; D020719:Glucuronides; C067342:dicentrine