title: Metabolism of diethyl 4-[(4-bromo-2-cyanophenyl)-carbamoyl]benzylphosphonate in the rat.
abstract: 1. The metabolism of diethyl 4-[(4-bromo-2-cyanophenyl)carbamoyl]benzylphosphonate (NO-1886), an antilipidaemic agent, was evaluated in the rat. 2. 14C-NO-1886 was dosed orally to rats (3 mg/kg) and within 24 h after dosing, 27.9 +/- 2.1 and 63.5 +/- 4.2% of the administered radioactivity was recovered from urine and faeces respectively. 3. The metabolite M-2 was isolated from the urine and faeces, and two other metabolites, M-3 and M-5, were isolated from the urine. Two of them were identified as ethyl 4-[(4-bromo-2-cyanophenyl)carbamoyl]benzylphosphonate (M-2) and 4-[(diethoxy-phosphoryl)methyl)]benzoic acid (M-3), and the other one was considered to be 2-amino-5-bromo-3-cyanobenzene sulphate (M-5) by ms and nmr spectrometry. 4. The major metabolic pathway of NO-1886 was found to be mono-hydrolysis of the diethyl phosphonate. It was also considered that M-5 may have been formed in vivo via 2-amino-5-bromo-benzonitrile (M-1) and 2-amino-5-bromo-3-hydroxybenzonitrile (M-4).
authors.affiliation: Laboratory of Drug Metabolism Research, Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Morioka
authors.forename: M
authors.initials: M
authors.lastname: Ohmizo
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.forename: S
authors.initials: S
authors.lastname: Naito
authors.forename: K
authors.initials: K
authors.lastname: Tsutsumi
mesh_terms: D000818:Animals; D001549:Benzamides / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics*; D001554:Benzene / Q000737:chemistry; D002250:Carbon Radioisotopes; D002845:Chromatography; D005243:Feces / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001549:Benzamides; D002250:Carbon Radioisotopes; D009943:Organophosphorus Compounds; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D001554:Benzene