SC-46275: a potent, long-acting gastric antisecretory prostaglandin with low oral bioavailability in the dog.
The synthetic prostaglandin, SC-46275, an omega chain cyclopentenyl analog of enisoprost, was studied to determine its gastric antisecretory potency and duration of action in meal-stimulated innervated (Pavlov) pouch dogs and its p.o. bioavailability in unoperated fasted dogs. SC-46275 exhibited potent antisecretory activity when administered directly into the gastric pouch, the ED50 being 0.01 micrograms/kg. It had a long duration of antisecretory action; significant (P less than or equal to .05) inhibition of total acid output was observed 16 hr after intrapouch administration of 0.03 micrograms/kg. At this dose p.o., neither SC-46275 nor its free acid metabolite was detected in plasma. These data indicate that SC-46275 has novel properties: it is a potent, long-acting gastric antisecretory agent which is not readily available systemically after p.o. administration. Thus, potential systemic side effects are expected to be absent or minimized at doses of SC-46275 which inhibit gastric acid secretion, and therefore it might be useful in peptic ulcer disease.
Perkins
W E
WE
Gastrointestinal Diseases Research, Searle Research and Development, Skokie, Illinois.
Burton
E G
EG
Tsai
B S
BS
Collins
P W
PW
Casler
J J
JJ
Gasiecki
A F
AF
Bauer
R F
RF
Jones
P H
PH
Gaginella
T S
TS
D000284:Administration, Oral; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium
D000897:Anti-Ulcer Agents; D014316:Tritium; C072122:SC-46275; D000527:Alprostadil