We studied the effects of 15(R)-15-methyl
prostaglandin E2 (
arbaprostil) on gastric secretion and various acute and chronic gastric lesions produced in rats.
Arbaprostil significantly inhibited gastric secretion in 4 hr-pylorus-ligated preparations when given intraduodenally in a dose of 30 or 100 micrograms/kg. The agent, however, significantly stimulated gastric secretion of rats with either a ligated or intact pylorus when given orally in doses of 3-100 micrograms/kg. Orally administered
arbaprostil dose-dependently prevented the development of HCI-
ethanol-,
histamine-, water-immersion stress-, or
indomethacin-induced gastric erosions. Intraduodenally administered
arbaprostil also dose-dependently prevented the development of
aspirin-induced gastric erosions in pylorus-ligated rats.
Arbaprostil, given orally in doses of 1-100 micrograms/kg twice daily for 2 weeks, had little or no effect on the healing of
acetic acid-induced
gastric ulcers. However,
oral administration of the agent in a dose of 3 or 10 micrograms/kg twice daily for 4 weeks significantly accelerated the healing of
acetic acid-induced
gastric ulcers. The increase in doses up to 100 micrograms/kg twice daily for 4 weeks had no effect on
ulcer healing. These results indicate that
arbaprostil, at either antisecretory or even
acid stimulating doses, is effective in preventing the development of acute gastric erosions and in accelerating the healing of chronic
gastric ulcers.