arbaprostil and Diarrhea

To determine the efficacy of single nighttime doses of arbaprostil [15(R)-15-methyl prostaglandin E2], 50 or 100 micrograms for 4 wk, a double-blind randomized placebo-controlled multiclinic trial was undertaken. Success was defined as complete healing of the ulcer documented by endoscopy. Fifty-one of 64 patients enrolled were considered evaluable. Ulcer healing was documented in 64.3%, 85.7%, and 31.2% of the 100-micrograms arbaprostil, 50-micrograms arbaprostil, and placebo treatment groups (p value vs. placebo = 0.003 and 0.002, respectively). No difference in side effects or changes in laboratory parameters were found between the treatment groups except that diarrhea, usually mild, was found more often in the 100-micrograms arbaprostil group (60.0%) than in the 50-micrograms arbaprostil (31.8%) or placebo groups (23.5%) (p value 100 micrograms arbaprostil vs. placebo = 0.02). A single nighttime administration of arbaprostil seems to be a safe and efficacious agent for the treatment of acute duodenal ulcer.

Topics: Adult; Arbaprostil; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Duodenal Ulcer; Humans; Male; Multicenter Studies as Topic; Prostaglandins E, Synthetic; Random Allocation

A multicenter study was conducted on 173 patients with active, endoscopically proven duodenal ulcers (158 men, 15 women). They were randomly assigned, in a double-blind manner, to two groups: those receiving placebo capsules (91 patients) and those receiving capsules containing 100 microgram of 15(R)-15-methyl prostaglandin E2 (arbaprostil) (82 patients). Each drug was ingested four times a day (1 h before meals and at bedtime) for 28 days. Endoscopy was performed on days 0, 14, and 28 after the trial began. At each examination, the ulcer size was measured and whether the ulcer had healed was recorded. Arbaprostil increased the incidence of ulcer healing to approximately the same degree as reported in most extensive studies with cimetidine. At 14 days, three times as many patients were totally healed in the arbaprostil-treated as in the placebo-treated group (37% vs. 12%, p less than 0.001). At 28 days, 67% of patients receiving arbaprostil were healed compared with 39% in the group receiving placebo (p less than 0.001). Similarly, the ulcer size, measured endoscopically, was much smaller after arbaprostil administration than in the group receiving placebo after both 14 and 28 days (p less than 0.001). Side effects attributable to treatment consisted primarily of loose stools and diarrhea (34%). Smoking retarded healing in the placebo-treated group (p less than 0.05), but did not significantly retard healing in patients treated with arbaprostil. We conclude that arbaprostil markedly accelerates the healing rate of active duodenal ulcers. This effect may be due to inhibition of acid secretion as well as gastric cytoprotection.

Topics: Adolescent; Adult; Aged; Arbaprostil; Cimetidine; Clinical Trials as Topic; Diarrhea; Double-Blind Method; Duodenal Ulcer; Endoscopy; Female; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Time Factors

The gastric antisecretory activity of 15(R)-15-methylprostaglandin E2 (arbaprostil) was compared with that of natural prostaglandin (PG) E2 in Pavlov pouch dogs. Arbaprostil significantly inhibited pentagastrin- and food-stimulated gastric secretion when it was administered directly into the pouch at a dose of 10-30 micrograms/pouch and 30-300 micrograms/pouch, respectively. Natural PGE2, however, was inactive up to 1000 micrograms/pouch. The data indicate that arbaprostil is a potent, long-acting orally active antisecretory drug that may be useful for the treatment of peptic ulcer disease.

Topics: Animals; Arbaprostil; Diarrhea; Dinoprostone; Dogs; Eating; Female; Gastric Acid; Gastric Mucosa; Male; Pentagastrin; Vagus Nerve

A stereospecific synthesis and the gastric antisecretory and diarrheal activity of a 3E,5Z diene analogue of misoprostol are described. The key intermediate in the synthesis was an alpha chain truncated acetylene that was obtained by a cuprate/enolate capture procedure on the corresponding cyclopentenone. Palladium-catalyzed coupling of the acetylene with methyl 4-iodo-3(E)-butenoate provided the conjugated enyne. Although selective hydrogenation of the enyne with Lindlar catalyst failed, the desired 3E,5Z diene was obtained with P-2 nickel as catalyst. The diene was about 3 times more potent than misoprostol in inhibiting gastric acid secretion in dogs and also in producing diarrhea in rats.

Topics: Alprostadil; Animals; Arbaprostil; Diarrhea; Dogs; Gastric Juice; Indicators and Reagents; Magnetic Resonance Spectroscopy; Male; Misoprostol; Prostaglandins E, Synthetic; Rats; Structure-Activity Relationship