Metabolism of diltiazem. I. Structures of new acidic and basic metabolites in rat, dog and man.

• DOI: 10.1248/bpb1978.11.211
• Publication Date: 2011-11-24T04:39:20Z
• Authors: Yoichi SUGAWARA; Motoaki OHASHI; Susumu NAKAMURA; Satoshi USUKI; Tatsuo SUZUKI; Yutaka ITO; Toshiyuki KUME; Shoichi HARIGAYA; Akio NAKAO; Mitsunori GAINO; Hirozumi INOUE
• Keywords: Male; 0301 basic medicine; Chemical Phenomena; Rats, Inbred Strains; Gas Chromatography-Mass Spectrometry; Rats; 3. Good health; Chemistry; Diltiazem; 03 medical and health sciences; Dogs; Species Specificity; Animals; Bile; Humans; Scintillation Counting; Chromatography, High Pressure Liquid

The metabolites of diltiazem in the urine rats, dogs and man rat bile were investigated. New including six acidic (A1-A6) four basic (M9, MB, MC, MD) isolated by high performance liquid chromatography their structures characterized gas chromatography-mass spectrometry. Acidic A1, A2, A3, A4 metabolite MD identified comparing properties with 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) N-didemethyl-diltiazem (MD). All have a CH2COOH group which may be formed oxidative deamination CH2CH2N (CH3)2 diltiazem.