Metabolism of roxatidine acetate hydrochloride. Liberation of deuterium from the piperidine ring during hydroxylation

Journal Article · Wed Jul 01 04:00:00 EDT 1987 · Drug Metab. Dispos.; (United States)

OSTI ID:5726233

Honma, S; Iwamura, S; Kobayashi, R; Kawabe, Y; Shibata, K

The metabolism of roxatidine acetate hydrochloride (RA), a new histamine-2 receptor antagonist, was studied by GC/MS in rats and dogs in vivo. The co-administration of /sup 14/C-RA and RA-d10 labeled with deuterium in the piperidine ring expedited the isolation and identification of 15 urinary metabolites. The major metabolites in both animals were M-1, M-8, M-10, and M-11; M-4 could be found only in the rat. The aromatic and piperidine ring-hydroxylated metabolites were found in small amounts in both species. Following the administration of RA-d10 to rats and dogs, oxygenated metabolites on the piperidine ring, such as M-3 and M-4, were isolated and their analysis indicated the unexpected loss of three or four deuterium atoms from the ring. Also, first and second isotope effects were observed on the conversion rate in vivo and retention time in HPLC, respectively.

• Research Organization: Teikoku Hormone Manufacturing Co., Ltd., Kanagawa, Japan
• OSTI ID: 5726233
• Journal Information: Drug Metab. Dispos.; (United States), Journal Name: Drug Metab. Dispos.; (United States) Vol. 15:4; ISSN DMDSA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
AZINES
CARBON 14 COMPOUNDS
CHROMATOGRAPHY
DEUTERIUM
DOGS
HETEROCYCLIC COMPOUNDS
HYDROGEN ISOTOPES
HYDROXYLATION
ISOTOPE APPLICATIONS
ISOTOPE EFFECTS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
METABOLISM
METABOLITES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIPERIDINES
PYRIDINES
RATS
RODENTS
SEPARATION PROCESSES
STABLE ISOTOPES
TRACER TECHNIQUES
VERTEBRATES