The metabolism of roxatidine acetate hydrochloride. Liberation of deuterium from the piperidine ring during hydroxylation.
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.
D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003903:Deuterium; D004285:Dogs; D008401:Gas Chromatography-Mass Spectrometry; D006635:Histamine H2 Antagonists / Q000378:metabolism*; D006900:Hydroxylation; D008297:Male; D010880:Piperidines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D006635:Histamine H2 Antagonists; D010880:Piperidines; D003903:Deuterium; C053742:roxatidine acetate