RT Journal Article
SR Electronic
T1 The metabolism of roxatidine acetate hydrochloride. Liberation of deuterium from the piperidine ring during hydroxylation.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 551
OP 559
VO 15
IS 4
A1 Honma, S
A1 Iwamura, S
A1 Kobayashi, R
A1 Kawabe, Y
A1 Shibata, K
YR 1987
UL http://dmd.aspetjournals.org/content/15/4/551.abstract
AB 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 14C-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.