The metabolism of etintidine in rat, dog, and human.
The metabolic fate of etintidine, a new H2-receptor antagonist, was studied in the rat, dog, and human. Following oral or iv administration of [14C]etintidine HCl to rats, 63-72% of the dose was eliminated in urine and 15-28% in feces over 3 days. In dogs, 52-70% of the administered dose was excreted in urine and 14-18% in feces over 5 days. In the urine of both species, the major portion (generally greater than 70%) of the radioactivity was associated with parent drug and its sulfoxide metabolite. In rats, a distinct sex-related difference in metabolism was observed following oral administration of 20 mg/kg doses, with males excreting nearly twice the amount of the sulfoxide relative to females. A significant sex-related difference in metabolism was not observed in dogs following oral administration of a comparable dose, nor was it observed in either species following iv drug administration. After oral administration of [14C]etintidine HCl to human volunteers, about 86% of the dose was recovered in urine and 13% in the feces over a 7-day period. In humans, the major urinary metabolite was the N'-glucuronide conjugate. Thus, sulfoxidation does not appear to be the major urinary metabolic pathway of the drug in humans, as it is in animals. The metabolic fate of etintidine and cimetidine, another H2-receptor antagonist, are compared in three species.
Wong
F A
FA
R. W. Johnson Pharmaceutical Research Institute, Ortho Pharmaceutical Corporation, Raritan, NJ 08869.
Lloyd
J R
JR
Graden
D W
DW
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002855:Chromatography, Thin Layer; D002927:Cimetidine / Q000378:metabolism; D004285:Dogs; D005243:Feces / Q000737:chemistry; D005260:Female; D006635:Histamine H2 Antagonists / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007093:Imidazoles / Q000378:metabolism* / Q000652:urine; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013056:Spectrophotometry, Ultraviolet
D006635:Histamine H2 Antagonists; D007093:Imidazoles; D002927:Cimetidine; C036616:etintidine