arbaprostil and Duodenal-Ulcer

Six hundred and thirty patients were enrolled in a randomized double-blind placebo-controlled trial evaluating two arbaprostil dosages (25 micrograms and 50 micrograms) qid for 4 wk for the treatment of acute duodenal ulcers. The healing rates in the placebo, 25-micrograms, and 50-micrograms treatment groups were 39%, 51%, and 60%, respectively. Smoking was found to adversely affect the healing rates in all the treatment groups. Pain severity was less with either arbaprostil treatment. The only side effect found was diarrhea: 10%, 14%, and 32% in the placebo, 25-micrograms, and 50-micrograms treatment groups, respectively. Severe diarrhea occurred in 1% of those patients who received the 50-micrograms dosage regimen, but in none of the other two groups. Arbaprostil at these two dosage levels, when given for 4 wk, appears to be a safe and efficacious agent for the treatment of acute duodenal ulcers.

Topics: Acute Disease; Arbaprostil; Capsules; Double-Blind Method; Duodenal Ulcer; Duodenoscopy; Female; Humans; Male; Multicenter Studies as Topic; Placebos; Prostaglandins E, Synthetic; Randomized Controlled Trials as Topic; Time Factors; Wound Healing

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

Topics: Arbaprostil; Autoradiography; Cell Division; Clinical Trials as Topic; Duodenal Ulcer; Gastric Mucosa; Humans; Prostaglandins E, Synthetic; Tritium

Previous therapeutic trials with prostaglandins have shown them to be effective in healing duodenal ulcers when used at doses that are highly effective suppressors of gastric acid secretion. We undertook this trial to determine if a cytoprotective dose of arbaprostil (10 micrograms q.i.d. for 4 wk) would also be efficacious in this disease state. Eighty-two patients between the ages of 19 and 72 yr with endoscopically documented duodenal ulcers were entered into this randomized double-blind placebo-controlled trial. The patients were monitored with biweekly endoscopies and laboratory examinations, weekly interviews during the period when drug was administered, and a follow-up interview plus laboratory examinations 1 wk after drug administration was completed. No statistically significant differences between the arbaprostil and placebo treatment groups were found for ulcer healing rates, pain relief, antacid consumption, side effects, or laboratory examinations. It is presumed that this prostaglandin may not have sufficient duodenal cytoprotective capacity to effectively heal duodenal ulcers, or that some suppression of gastric acid secretion may be required to achieve significant clinical efficacy.

Topics: Adult; Aged; Arbaprostil; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Random Allocation; Wound Healing

The efficacy of arbacet (a synthetic analog of prostaglandin E2) in definite cytoprotective but minimal antisecretory dose was evaluated in the treatment of duodenal ulcer. One hundred five patients with endoscopically proven duodenal ulcer were randomized in a double-blind manner to receive four times daily either arbacet 25 micrograms or placebo. Ulcer healing was assessed endoscopically after two and four weeks of treatment. The mean age, sex distribution, and tobacco and alcohol consumption were similar in the two treatment groups. The ulcers of 16 patients in both the placebo and the arbacet-treated group healed after 14 days of treatment. At the end of the study, healing of the ulcer was observed in 69.2% of the arbacet-treated patients and in 60.4% of patients in the placebo treated group. (Difference was not statistically significant). We conclude that cytoprotective doses of arbacet with minimal antisecretory properties are not effective in duodenal ulcer healing.

Topics: Adolescent; Adult; Aged; Arbaprostil; Drug Administration Schedule; Duodenal Ulcer; Female; Gastric Mucosa; Humans; Male; Middle Aged; Prostaglandins E, Synthetic

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

Basal and meal-stimulated serum gastrin with or without prior intake of 100 mcg 15(R)-15-methyl prostaglandin E2 (PG) in encapsulated form were measured in 40 patients with active duodenal ulcer disease at the start and at the end of a 4 week treatment period with 100 mcg PG q i d or placebo (Pl). Basal serum gastrin levels did not change throughout the study. Neither was there a blunting of the meal-stimulated serum gastrin release by PG as has been previously observed. The enhanced healing rate (68.4% during PG compared to 33.3% during Pl) can therefore not be explained by changes in basal or meal-stimulated serum gastrin.

Topics: Adult; Arbaprostil; Duodenal Ulcer; Eating; Female; Gastrins; Humans; Kinetics; Male; Middle Aged; Placebos; Prostaglandins E, Synthetic

Topics: Arbaprostil; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Humans; Prostaglandins E; Prostaglandins E, Synthetic

Topics: Animals; Arbaprostil; Drug Administration Schedule; Duodenal Ulcer; Humans; Intestinal Mucosa; Prostaglandins E, Synthetic; Wound Healing

The effects of a stable prostaglandin (PG) E2 analog (15-R-15 methyl PGE2) and aspirin, a potent inhibitor of cyclooxygenase, on modified sham-feeding (MSF)-stimulated gastric secretion and serum gastrin and pancreatic polypeptide (PP) levels were measured in patients with duodenal ulcer. PGE2 analog given orally significantly reduced gastric acid and pepsin secretion and suppressed serum PP but not gastrin responses to MSF. Suppression of PG generation in the gastric mucosa did not influence the secretory or hormonal responses to MSF. This study shows that endogenous PGs are not involved in the control of vagally stimulated gastric secretion, but exogenous PGE2 analog is an effective inhibitor of such secretion and merits clinical evaluation in the treatment of duodenal ulcer.

Topics: Adult; Arbaprostil; Aspirin; Duodenal Ulcer; Gastric Acid; Gastric Juice; Gastrins; Humans; Pepsin A; Prostaglandins E, Synthetic; Vagus Nerve

Topics: Animals; Arbaprostil; Cats; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Histamine; Pancreatic Juice; Pentagastrin; Pepsin A; Secretin