SC-46275: a potent, long-acting gastric antisecretory prostaglandin with low oral bioavailability in the dog.

Abstract

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.

• Authors: W E Perkins, E G Burton, B S Tsai, P W Collins, J J Casler, A F Gasiecki, R F Bauer, P H Jones, T S Gaginella
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 259 Issue 3 Pg. 1004-7 (Dec 1991) ISSN: 0022-3565 [Print] United States
• PMID: 1762057 (Publication Type: Journal Article)

Chemical References

• Anti-Ulcer Agents
• Tritium
• SC-46275
• Alprostadil

Topics

• Administration, Oral
• Alprostadil (analogs & derivatives, pharmacokinetics, pharmacology)
• Animals
• Anti-Ulcer Agents (pharmacokinetics, pharmacology)
• Biological Availability
• Dogs
• Dose-Response Relationship, Drug
• Female
• Gastric Mucosa (drug effects, metabolism)
• Tritium