Perkins W E, Burton E G, Tsai B S, Collins P W, Casler J J, Gasiecki A F, Bauer R F, Jones P H, Gaginella T S
Gastrointestinal Diseases Research, Searle Research and Development, Skokie, Illinois.
J Pharmacol Exp Ther. 1991 Dec;259(3):1004-7.
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.
对合成前列腺素SC - 46275（一种依尼前列素的ω链环戊烯基类似物）进行了研究，以确定其在进食刺激的有神经支配的（巴甫洛夫）小胃犬中的胃抗分泌效力和作用持续时间，以及在未手术的禁食犬中的口服生物利用度。将SC - 46275直接注入胃小囊时，它表现出强大的抗分泌活性，半数有效剂量（ED50）为0.01微克/千克。其抗分泌作用持续时间长；在胃小囊内给予0.03微克/千克后16小时，观察到总酸分泌受到显著（P≤0.05）抑制。口服该剂量后，在血浆中未检测到SC - 46275及其游离酸代谢物。这些数据表明，SC - 46275具有新特性：它是一种强效、长效的胃抗分泌剂，口服给药后不易进入全身循环。因此，在抑制胃酸分泌的SC - 46275剂量下，预计不会出现或最小化潜在的全身副作用，所以它可能对消化性溃疡疾病有用。
