title: Metabolism of diltiazem. I. Structures of new acidic and basic metabolites in rat, dog and man.
abstract: The metabolites of diltiazem in the urine of rats, dogs and man and rat bile were investigated. New metabolites including six acidic metabolites (A1-A6) and four basic metabolites (M9, MB, MC, MD) were isolated by high performance liquid chromatography and their structures were characterized by gas chromatography-mass spectrometry. Acidic metabolites A1, A2, A3, A4 and basic metabolite MD identified by comparing their properties with the synthetic compounds; (+)-(2S, 3S)-2-(4-methoxyphenyl)-3-acetoxy-4-oxo-2,3,4,5-tetrahydro-1,5- benzothiazepin-5-acetic acid (A1), 3-deacetyl-A1 (A2), O-demethyl-A1 (A3), O-demethyl-3-deacetyl-A1 (A4) and N-didemethyl-diltiazem (MD). All acidic metabolites have a CH2COOH group which may be formed by oxidative deamination of the CH2CH2N(CH3)2 group of diltiazem.
authors.affiliation: Biological Research Laboratory, Tanabe Seiyaku Co., Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sugawara
authors.forename: M
authors.initials: M
authors.lastname: Ohashi
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Usuki
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Kume
authors.forename: S
authors.initials: S
authors.lastname: Harigaya
authors.forename: A
authors.initials: A
authors.lastname: Nakao
authors.forename: M
authors.initials: M
authors.lastname: Gaino
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004110:Diltiazem / Q000378:metabolism* / Q000652:urine; D004285:Dogs; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012588:Scintillation Counting; D013045:Species Specificity
chemical_list: D004110:Diltiazem