enprostil and Stomach-Ulcer

Anti-ulcer prostaglandins (PG)--misoprostol, enprostil and rioprostil--have been given to more than 5000 patients in short-term studies on gastric and duodenal ulcer. Analysis of these studies shows the drugs to be safe. Their side effects appear to be dose-dependent and mainly restricted to the gastrointestinal system, the major syndromes being diarrhoea and abdominal pain. The clinical relevance of PG-related unwanted effects, though in average exceeding that of H2-blockers, seems to be sufficiently low. In terms of safety efficacy, however, they appear inferior to H2-antagonists, so their routine use in preference to the latter compounds is still premature.

Topics: Alprostadil; Anti-Ulcer Agents; Clinical Trials as Topic; Duodenal Ulcer; Enprostil; Humans; Misoprostol; Prostaglandins E; Prostaglandins E, Synthetic; Rioprostil; Stomach Ulcer

Topics: Alprostadil; Animals; Anti-Ulcer Agents; Duodenal Ulcer; Enprostil; Gastric Juice; Gastrins; Humans; Misoprostol; Omeprazole; Prostaglandins E, Synthetic; Stomach Ulcer

Topics: Alprostadil; Animals; Anti-Ulcer Agents; Duodenal Ulcer; Enprostil; Humans; Misoprostol; Prostaglandins E, Synthetic; Smoking; Stomach Ulcer

Conventional ulcer therapy has not been proven effective in healing gastric ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) if the NSAIDs are continued. Our objective in this study was to determine whether a prostaglandin analog is an effective treatment for such NSAID-induced lesions.. To make this determination, we conducted a 9-wk double-blind trial comparing placebo with enprostil 35 micrograms twice daily and three times daily. Use of antacids was not allowed. Three centers entered 145 patients with chronic inflammatory arthritis and osteoarthritis, mean age 63 yr, who required continuous fixed-dose NSAID therapy within the range of therapeutic dosage. The minimum entrance criterion was the presence of either four gastric erosions or one gastric ulcer. Two pretreatment endoscopies within a 2-wk interval were performed to establish the presence of stable baseline gastric lesions. Endoscopy was repeated at wk 6 and 9 during treatment. All groups were similar with regard to age distribution, sex, weight, height, smoking usage, and alcohol consumption.. The ulcer healing rates were 14%, 57%, and 68% at 6 wk and 19%, 68%, and 74% at 9 wk for the groups receiving placebo, enprostil twice daily, and enprostil three times daily, respectively (p < 0.01). Complete mucosal healing of all erosions and ulcers at 9 wk occurred in 59% of enprostil-treated patients and in 10% of placebo-treated patients. Additional gastric erosions and gastric ulcers developed in 16% of placebo patients and 4% of the enprostil patients. Eighteen percent of enprostil patients withdrew early from the study due to adverse experiences, such as diarrhea and abdominal pain.. We concluded that during continued NSAID therapy 1) enprostil 35 micrograms (taken either twice daily or three times daily) heals NSAID-induced gastric ulcers and erosions and protects the mucosa from further NSAID-induced gastric injury; 2) gastric ulcers and erosions rarely heal spontaneously, and 3) enprostil results in a high incidence of diarrhea.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Enprostil; Female; Gastric Mucosa; Humans; Male; Middle Aged; Osteoarthritis; Stomach Ulcer

Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers.

Topics: Antacids; Double-Blind Method; Enprostil; Female; Humans; Male; Middle Aged; Prospective Studies; Prostaglandins E, Synthetic; Ranitidine; Recurrence; Stomach Ulcer; Wound Healing

In a double-blind, multicentre study 77 patients with benign gastric ulcer were randomly allocated to treatment with either enprostil 35 micrograms bd or pirenzepine 50 mg bd. After four weeks of treatment 13/26 (50 per cent) of evaluable enprostil-treated patients and 9/30 (30 per cent) of evaluable pirenzepine-treated patients were healed. Corresponding healing figures after eight weeks were 20/25 (80 per cent) and 25/31 (81 per cent). Both drugs rapidly reduced the severity of ulcer pain and the need for antacid use. No statistically significant differences were detected between the treatments with respect to healing rate or symptom control. Adverse events were reported by eight patients taking enprostil and by 17 patients taking pirenzepine. Two patients withdrew from each treatment group because of adverse events. None of these was serious. In conclusion, enprostil and pirenzepine were equally effective in healing gastric ulcers and no statistically significant differences in safety and efficacy were detected. There was a tendency for earlier healing and fewer side effects in the enprostil-treated patients.

Topics: Adolescent; Adult; Aged; Double-Blind Method; Enprostil; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Pirenzepine; Prostaglandins E, Synthetic; Randomized Controlled Trials as Topic; Stomach Ulcer

Enprostil is a synthetic dehydro-prostaglandin E2 with gastroduodenal ulcer-healing and mucosal-protective properties. One hundred and three healthy volunteers were randomized to receive capsules of enprostil 35 micrograms b.d. (the clinically recommended dose), enprostil 70 micrograms b.d., or placebo b.d. All underwent endoscopic assessment of the gastroduodenal mucosa, scored using a 0-4 scale, at baseline and on Days 3, 7, 14, 21 and 28 of dosing. Mean and median maximum scores demonstrated a dose response, and the mean maximum scores were statistically significantly higher for both enprostil groups on each endoscopy day when compared with placebo. The majority of enprostil-treated subjects had petechial haemorrhages. The proportion of volunteers with small white-based mucosal breaks (erosions) was significantly higher for the fundus in the enprostil 70-microgram group on Days 21 and 28 when compared with placebo, but there were no significant differences between treatment groups for any area on the other study days. The 70-microgram dose was associated with significantly more gastrointestinal adverse events than the 35-microgram dose, which was similar to placebo. There were no significant differences between groups for large white-based mucosal breaks (ulcers). We conclude that oral enprostil produced gastric mucosal petechial haemorrhages, primarily in the fundus of the stomach. Gastric mucosal petechial haemorrhages are probably without clinical significance because they are very common in the general population (10-15%) and do not progress to erosions and ulcers.

Topics: Double-Blind Method; Duodenum; Enprostil; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Intestinal Mucosa; Male; Reference Values; Salicylates; Salicylic Acid; Stomach Ulcer

In a randomly allocated, double-blind, endoscopically controlled study, 98 patients with gastric ulcers were treated with either (a synthetic prostaglandin of E2-like structure) enprostil 70 micrograms b.d. or 150 mg ranitidine b.d. The healing rates at 4, 8 and 12 weeks were enprostil 57, 91 and 94% and for ranitidine 55, 88 and 98%, respectively. Following ulcer healing, half the patients were followed for 1 year without treatment and the others were given 70 micrograms enprostil nocte. Endoscopy was repeated in both groups after 6 and 12 months or if dyspeptic symptoms returned. The recurrence rate without maintenance at 6 and 12 months, following ranitidine therapy, was 67 and 75%, and after enprostil therapy 50 and 61%, respectively. On maintenance enprostil, the recurrence rates were 28 and 40%. Forty-seven per cent of patients who completed maintenance treatment had a proven ulcer recurrence within 6 months of stopping therapy. Diarrhoea was a common side-effect of enprostil therapy. Seven patients were withdrawn because of diarrhoea or abdominal pain.

Topics: Double-Blind Method; Endoscopy, Gastrointestinal; Enprostil; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ranitidine; Recurrence; Stomach Ulcer

One hundred twenty-seven patients with endoscopically diagnosed active duodenal, pyloric, or prepyloric ulcers participated in this multicenter, double-blind, randomized, controlled trial comparing placebo with enprostil 35 micrograms twice daily for up to four weeks. Cumulative endoscopic healing for the enprostil and placebo treatment groups, respectively, was 25% (15 of 59) and 12% (7 of 60) at two weeks (P = 0.060) and 59% (34 of 58) and 33% (19 of 57) at four weeks (P = 0.005). Excluding prepyloric ulcers, cumulative healing for the enprostil and placebo groups, respectively, was 22% (9 of 41) and 7% (3 of 44) at two weeks (P = 0.104) and 56% (23 of 41) and 24% (10 of 42) at four weeks (P = 0.002). A greater percentage of prepyloric ulcers healed on enprostil than placebo, but the difference was not significant. Mean antacid use in both groups was identical, averaging only two or less tablets per day in each group throughout the study. Daytime pain was relieved more quickly in the enprostil group, while median time to relief of nighttime pain was essentially identical in both groups. The most common side effect in the enprostil treatment group, diarrhea, was mostly mild to moderate in intensity and was generally self-limiting, requiring no specific therapy; no patient withdrew because of this complaint. Other symptoms and laboratory profiles were similar in the two groups. These results indicate that enprostil 35 micrograms taken twice daily for four weeks is effective and safe for the treatment of prepyloric, pyloric channel, and duodenal ulcers.

Topics: Adult; Aged; Aged, 80 and over; Clinical Trials as Topic; Diarrhea; Double-Blind Method; Drug Administration Schedule; Duodenal Ulcer; Enprostil; Esophagoscopy; Female; Gastroscopy; Humans; Male; Middle Aged; Multicenter Studies as Topic; Prostaglandins E, Synthetic; Pylorus; Random Allocation; Smoking; Stomach Ulcer

Anti-ulcer prostaglandins (PG)--misoprostol, enprostil and rioprostil--have been given to more than 5000 patients in short-term studies on gastric and duodenal ulcer. Analysis of these studies shows the drugs to be safe. Their side effects appear to be dose-dependent and mainly restricted to the gastrointestinal system, the major syndromes being diarrhoea and abdominal pain. The clinical relevance of PG-related unwanted effects, though in average exceeding that of H2-blockers, seems to be sufficiently low. In terms of safety efficacy, however, they appear inferior to H2-antagonists, so their routine use in preference to the latter compounds is still premature.

Topics: Alprostadil; Anti-Ulcer Agents; Clinical Trials as Topic; Duodenal Ulcer; Enprostil; Humans; Misoprostol; Prostaglandins E; Prostaglandins E, Synthetic; Rioprostil; Stomach Ulcer

Prostanoids decrease gastric acid secretion and exert cytoprotective properties. The effect of several synthetic prostanoids on gastric ulcer healing was evaluated. The first trials were performed on a small number of patients with PGE2 analogs and their results were inconclusive. Two huge multicenter trials tested the efficacy of misoprostol, a synthetic PGE1 analog, in comparison to placebo and cimetidine. In the placebo-controlled trial, following 8 weeks of therapy, misoprostol 100 micrograms q.i.d was significantly better than placebo. In the cimetidine controlled trial, 2 doses of misoprostol were tested, 50 micrograms and 200 micrograms q.i.d. Ulcer healing rates following 4 weeks were 39%, 51%, and 58% in the misoprostol 50 micrograms, 200 micrograms, and cimetidine treatment groups, respectively. There was no statistically significant difference in the healing rates at 4 weeks between the misoprostol 200 micrograms and cimetidine 300 mg q.i.d groups (P = 0.16). The healing rate with the misoprostol 200 micrograms dose was significantly better than with the 50 micrograms dose (P = 0.008). Cimetidine 300 mg relieved global pain significantly better than misoprostol 200 micrograms at 2 weeks (P = 0.047) but not at 4 weeks. The 200 micrograms dose of misoprostol relieved pain significantly better than the 50 micrograms dose at 4 weeks (P = 0.019), but not at 2 weeks. All 3 treatments were well tolerated. Severe adverse events were rare. The efficacy of enprostil, another PGE2 analog, on gastric ulcer healing was also found to be better than placebo and not significantly different from ranitidine. The synthetic prostanoids, misoprostol and enprostil, appear to be safe and effective in the treatment of gastric ulcer.

Topics: Adolescent; Adult; Aged; Alprostadil; Anti-Ulcer Agents; Bicarbonates; Cimetidine; Clinical Trials as Topic; Enprostil; Female; Gastric Acid; Gastric Mucosa; Humans; Male; Middle Aged; Misoprostol; Pepsin A; Prostaglandins; Prostaglandins E, Synthetic; Ranitidine; Smoking; Stomach Ulcer

In a randomized, endoscopically controlled double-blind trial the effectiveness of a twice daily dose of the prostaglandin E2-analogue enprostil was compared with ranitidine given to 93 ambulatory patients with benign gastric ulcers. Under 35 micrograms b.i.d. enprostil the ulcer healing rates after 2, 4, 6 and 8 weeks averaged 22% (10/46), 58% (26/45), 80% (35/44) and 86% (37/43). The corresponding values for ranitidine 150 mg b.i.d. were 22% (10/46), 66% (29/44), 84% (38/45) and 89% (41/46). The differences were not statistically significant. Both drugs had a similar influence on the ulcer symptoms and were well tolerated. The findings suggest that enprostil can be given in a twice daily dosage in the treatment of benign gastric ulcers.

Topics: Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Enprostil; Humans; Prostaglandins E, Synthetic; Random Allocation; Ranitidine; Smoking; Stomach Ulcer; Wound Healing

This study evaluated the efficacy of two dosage levels of enprostil in 129 patients with gastric ulcer disease. Patients with endoscopically diagnosed gastric ulcer were randomly assigned to receive enprostil 70 micrograms, enprostil 35 micrograms, or a matching placebo capsule twice daily for six weeks. Ulcer healing rates were similar in all treatment groups after two weeks of therapy, but began to show some differences in favor of the enprostil treatment groups after four weeks. Greater differences were noted after six weeks of therapy, with healing rates of 70 percent in the 70-micrograms enprostil group, 82 percent in the 35-micrograms enprostil group, and 50 percent in the placebo group. The six-week healing rate in the 35-micrograms enprostil group was significantly greater than the placebo rate (p = 0.005). Comparison of healing rates in the active treatment groups and the placebo group after six weeks of therapy showed a correlation between therapeutic effect and ulcer size at baseline. This trend is illustrated by a 24 percent difference between the 35-micrograms enprostil group and the placebo group among patients with small (3 to 9 mm) ulcers, compared with a 46 percent difference between these two groups among patients with large (20 to 30 mm) ulcers. Thus, the effectiveness of enprostil is more readily demonstrable in patients with larger ulcers.

Topics: Adult; Clinical Trials as Topic; Endoscopy; Enprostil; Female; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Random Allocation; Stomach Ulcer; Time Factors

In a randomized, double-bind, parallel, multi-clinic study, the safety and efficacy of enprostil (35 micrograms twice daily) and ranitidine (150 mg twice daily) were compared in the treatment of active gastric ulcer in 93 outpatients (47 enprostil-treated patients and 46 ranitidine). The two treatment groups were well matched for demographic characteristics. The healing rates in the enprostil group were 22, 58, 80, and 86 percent at two, four, six, and eight weeks, respectively. The corresponding rates in the ranitidine group were 22, 66, 84, and 89 percent. None of these differences was statistically significant. The area of the ulcer at baseline and smoking status did not appear to influence healing rates. There were no significant differences between treatment groups in time to relief of ulcer symptoms, frequency of daytime or nighttime ulcer pain, or antacid use. Side effects attributable to enprostil treatment were diarrhea (10 percent versus 6 percent with ranitidine), gastrointestinal pain, and vomiting. These side effects, however, did not influence the patients' assessments of their overall response to enprostil and ranitidine therapy. Six enprostil-treated patients and one ranitidine-treated patient withdrew from the trial prematurely because of adverse experiences. Monitoring of clinical laboratory test results showed no significant changes in the two treatment groups. This study demonstrates that a prostaglandin E2 analogue, enprostil, in a dose of 35 micrograms twice daily, is similarly safe and effective as ranitidine in the treatment of active gastric ulcer.

Topics: Adolescent; Adult; Aged; Antacids; Clinical Trials as Topic; Double-Blind Method; Enprostil; Female; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Random Allocation; Ranitidine; Smoking; Stomach Ulcer; Time Factors

Gastric ulcers in children are often seen as a result of an imbalance between nocive factors and the resistance of the mucosa. Glanzmann's thromboastenia is a defect in platelet aggregation and its nature may be associated to local factors which precipitate or perpetuate bleeding. Prostaglandins are hormones of local action which inhibit the secretion of acid and therefore protect the mucosa. We report a case of an 18 year old male youngster with Glanzmann's thromboastenia and a gastric ulcer previously unsuccessfully treated with cimetidine, aluminum hydroxide solution, ranitidine, sucralfate and later controlled with PGE2. In sum, the usefulness of the cytoprotecting effects of the prostaglandins are successfully evaluated in a young man with platelet aggregation abnormalities.

Topics: Adolescent; Anti-Ulcer Agents; Chronic Disease; Enprostil; Humans; Male; Prostaglandins E, Synthetic; Stomach Ulcer; Thrombasthenia

Topics: Animals; Aspirin; Enprostil; Female; Gastric Mucosa; Male; Mucus; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Sex Factors; Stomach Ulcer

Prostaglandins of the E series have been shown, both in animals and humans to produce gastrointestinal antisecretory and antiulcer effects. Enprostil, a modified allenic prostaglandin E was found to be a highly potent inhibitor of gastric HCl secretion in a variety of species. In rats, in which both the pylorus and esophagus were ligated, p.o. ED50 values and 95% CL for inhibiting acid secretion evoked by histamine, pentagastrin and carbachol were 9.9 (6.7-15), 40 (11-145) and 0.83 (0.78-0.89) micrograms/kg, respectively. In inhibiting histamine-evoked acid secretion, enprostil was more potent when administered p.o. than when injected into the duodenum or s.c. When enprostil was injected directly into the pouch of Heidenhein dogs, intense antisecretory activity occurred, ED50 = 0.9 (0.7-1.1) micrograms/kg, whereas, when given p.o. to the main stomach the ED50 was 6.6 (3.2-13.6) micrograms/kg. Administration of cimetidine either p.o. or to the pouch resulted in virtually identical ED50 values, viz., 2.9 and 3.1 mg/kg. Enprostil also inhibited dimaprit- and pentagastrin-induced acid secretion in cats with permanent gastric fistulae. The oral ED50 values for inhibiting acid secretion evoked by these two secretagogues were 2.5 (1.4-4.3) and 0.8 (0.5-1.5) micrograms/kg, respectively. Enprostil was extremely potent in preventing indomethacin plus "cold stress" ulcers in rats. When given orally the ED50 was 0.61 (0.31-1.22) and s.c. it was 22 (9.0-52) micrograms/kg. It was also highly potent in preventing cysteamine-induced duodenal ulcers when given p.o., ED50 = 20 (17-23) micrograms/kg. Thus, enprostil is a highly potent antisecretory and antiulcer agent. It appears to act topically; directly at gastric mucosal sites.

Topics: Animals; Atropine; Cardiovascular System; Cats; Cysteamine; Dinoprostone; Dogs; Duodenal Ulcer; Enprostil; Fasting; Female; Gastric Emptying; Gastric Mucosa; Male; Metiamide; Prostaglandins E; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Stomach Ulcer; Uterine Contraction