enprostil and Duodenal-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

We conducted a clinical trial to compare the efficacy and safety profile of two prostaglandin analogues, enprostil (35 micrograms twice daily) and misoprostol (200 micrograms four times daily) in the treatment of acute duodenal ulcers in 214 patients. The two agents healed approximately 80% and in excess of 90% of duodenal ulcers after 4 and 6 weeks' therapy, respectively. There was a significantly lower ulcer healing rate in both treatment groups in smokers compared with non-smokers (P < 0.05). However, daytime and nighttime ulcer pain relief was achieved in fewer than 50% of patients by either agent. Diarrhea, which occurred in more than 40% of patients, was the predominant side effect, and occurred mainly during the first 2 weeks of therapy with either agent. Nevertheless, this side effect was mild and self-limiting in the majority of patients. Both agents were found to be safe and well tolerated by the majority of patients. We conclude that these prostaglandin analogues are safe and effective duodenal ulcer healing agents. Furthermore, there was very little difference between enprostil and misoprostol. The limiting factors, however, for their routine use as ulcer healing agents are their low efficacy with regard to ulcer pain relief and the high incidence of diarrhea.

Topics: Acute Disease; Adult; Aged; Analysis of Variance; Anti-Ulcer Agents; Duodenal Ulcer; Endoscopy, Digestive System; Enprostil; Female; Humans; Male; Middle Aged; Misoprostol; Pilot Projects; Single-Blind Method

Enprostil, a synthetic prostaglandin E2, has been shown to exert both antisecretory and mucoprotective activity. It is effective in duodenal ulcer healing. OBJECTIVE--This study was performed to compare the frequency and the delay of spontaneous duodenal ulcer relapse during a two-year follow up period after initial healing by enprostil (35 micrograms, twice a day) or ranitidine (300 mg per day). METHODS--This multicentric, double-blind, randomized study included 642 patients (324 in the enprostil group and 318 in the ranitidine group). Patients included in the follow up period were evaluated by an endoscopy at 6 months, one and two years after healing. RESULTS--After a 6 weeks treatment period, healing rate was 85% for ranitidine and 70% for enprostil, respectively (P < 0.001). Adverse effects, especially digestive ones, occurred more often with enprostil than with ranitidine (P < 0.001). After initial healing, there was no significant difference between the 2 groups concerning the cumulative rate of relapse, despite a non significant trend for a milder rate of relapse in the enprostil group (P = 0.08). Twenty-seven % of the patients randomized to treatment (intend-to-treat analysis) in the enprostil group and 29% in the ranitidine group had no ulcer recurrence 6 months after ulcer healing, and respectively 12% and 13% at 2 years (difference not statistically significant). CONCLUSIONS--It is concluded that a) ranitidine is more effective and has less adverse effects than enprostil for duodenal ulcer healing, b) after duodenal ulcer healing by enprostil, there is a non significant trend for a lower rate of relapse than after healing with ranitidine, c) there is the same proportion of patients without ulcer in the 2 groups after 6 months and 2 years.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Endoscopy, Digestive System; Enprostil; Female; Humans; Male; Middle Aged; Prospective Studies; Radiography; Ranitidine; Recurrence

Enprostil, a synthetic E2-prostaglandin efficacious for duodenal ulcer healing, presents both antisecretory and antigastrinic effects. This is at variance with the elevation of plasma gastrin observed with ranitidine. OBJECTIVE--This leads us to compare enprostil and ranitidine on the following points: a) variations of plasma gastrin (basal and postprandial) parameters over a 6-week conventional treatment; b) correlation studies between ulcer relapses (frequency and temporal evolution) after treatment discontinuation and various gastrinic criteria. METHODS--Among a group of 642 patients followed for ulcer relapse, 165 were considered for gastrin (78 of the "Enprostil" group and 87 of the "Ranitidine" group). RESULTS--Initially, both populations were comparable for clinical and plasma gastrin parameters. After 6 weeks of treatment, the increases in the various gastrin parameters (basal, postprandial, peak, integraded) were significantly greater and the absolute values higher (Wilcoxon, P < 0.001) with ranitidine than with enprostil. No correlation was found between relapse occurrence after drug discontinuation and these gastrin parameters. CONCLUSIONS--Ranitidine hypergastrinemia seems directly related to gastric hyposecretion whereas its absence with enprostil is likely more dependent upon a specific antigastrinic activity than on a reduced antisecretory activity. Those differences in mechanism of action have no consequence on the stability of ulcer obtained by either drug.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Enprostil; Female; Gastrins; Humans; Male; Middle Aged; Prospective Studies; Ranitidine; Recurrence

The effect of gastric emptying of two doses (35 and 70 micrograms) of enprostil given orally was evaluated in eight patients with endoscopically confirmed duodenal ulcer. Gastric emptying of a radiolabelled solid meal was assessed with the use of a gamma camera. Enprostil dose-dependently accelerated gastric emptying of solids; the gastric emptying index, Ix, increased from 1.62 +/- 0.38 min-1.10(-2) after placebo to 2.77 +/- 0.56 min-1.10(-2) after 35 micrograms enprostil (p less than 0.05 versus placebo) and to 3.65 +/- 0.64 min-1.10(-2) after 70 micrograms enprostil (p less than 0.005 versus placebo). The fraction of the radiolabelled food retained in the stomach at the end of the gastric emptying examination (that is, after 90 min) amounted to 50.5 +/- 6.9% after placebo, 35.2 +/- 7.4% after 35 micrograms enprostil, and 24.1 +/- 8.4% after 70 micrograms enprostil. It is concluded that enprostil elicits a significant speeding up of solid-phase gastric emptying in duodenal ulcer patients.

Topics: Administration, Oral; Adult; Double-Blind Method; Duodenal Ulcer; Enprostil; Food; Gastric Emptying; Gastrointestinal Motility; Humans; Male; Middle Aged; Prostaglandins E, Synthetic

Enprostil, a synthetic PGE2, has been shown to have an inhibitory effect on gastric acid secretion, a mucoprotective effect and a postprandial lowering effect on gastrin. A double blind randomized study was performed in 80 patients, in order to evaluate the efficacy and safety enprostil (35 mu b.i.d) as compared to cimetidine (400 mg b.i.d) in duodenal ulcer. Healing rates after two, four and six weeks of treatment, as based on endoscopic evaluation, were 35, 72 and 83 p. 100 for enprostil and 45, 73 and 83 p. 100 for cimetidine, respectively. There were no significant differences between treatment groups. The time to relief of nighttime and daytime ulcer pain and antacid consumption were similar in the two groups. The patient's overall subjective assessment was better in the cimetidine group, but this was not confirmed by physicians' opinions. Diarrhea was observed in 7 p. 100 of patients treated by enprostil compared with 5 p. 100 for patients treated by cimetidine. One enprostil treated patient withdrew from the trial prematurely because of abdominal pain. This study demonstrates the efficacy and safety of enprostil in the treatment of active duodenal ulcer at the dosage of 35 micrograms twice daily.

Topics: Adult; Cimetidine; Double-Blind Method; Duodenal Ulcer; Enprostil; Female; Humans; Male; Multicenter Studies as Topic; Prostaglandins E, Synthetic; Random Allocation

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

Enprostil, a prostaglandin E2 analogue, is effective in healing acute duodenal ulcer but its value in preventing recurrence, when given daily for maintenance therapy, is uncertain. In this three-centre study we compared enprostil and ranitidine maintenance therapy; the latter is known to reduce duodenal ulcer relapse rates. Patients whose duodenal ulcers had been healed by treatment with an H2-receptor antagonist were randomized to receive single-blind treatment with either 35 micrograms enprostil (n = 64) or 150 mg ranitidine (n = 64) at bedtime for periods of up to 1 year. Endoscopy was routinely performed at 3 months at one centre, and at 6 and 12 months at all three centres, or whenever ulcer symptoms recurred. Clinical assessment and laboratory investigations were performed every 3 months. Relapse, defined as recurrent ulcer with or without pain, or erosions with pain, was significantly greater in patients on enprostil, the comparative rates at 3, 6 and 12 months were: enprostil 23, 31 and 36% ranitidine 6, 12 and 17% (P = 0.013; P = 0.03 and P = 0.03, respectively). Thirty-one patients reported adverse events, the most common being headache (enprostil = 6, ranitidine = 2) and mild diarrhoea (enprostil = 6, ranitidine = 0). Four patients on enprostil were withdrawn for adverse events, although none terminated because of diarrhoea. There were no clinically significant changes in haematology or biochemistry. Enprostil may reduce duodenal ulcer relapse but at a dose of 35 micrograms nightly, it is less effective than 150 mg ranitidine nightly.

Topics: Adult; Aged; Aluminum Hydroxide; Drug Combinations; Duodenal Ulcer; Endoscopy, Gastrointestinal; Enprostil; Female; Humans; Magnesium Hydroxide; Male; Middle Aged; Pain; Ranitidine; Recurrence; Single-Blind Method; Smoking

Topics: Adult; Double-Blind Method; Drug Evaluation; Duodenal Ulcer; Enprostil; Female; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Random Allocation

In a multicentre trial, 120 patients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with either 35 micrograms enprostil b.d. or 400 mg cimetidine b.d. for up to 6 weeks on a double-blind basis. After 6 weeks, 82% (42/51) of enprostil-treated patients and 92% (44/48) of cimetidine-treated patients were healed. Corresponding healing figures on an intention-to-treat basis were 70% and 76%. No significant differences were detected between treatments with respect to healing rates or symptom control at any time. Side-effects were reported by 14 patients taking enprostil and 17 patients taking cimetidine; none were serious but they resulted in withdrawal of one and two patients respectively. Enprostil was found to be similar in efficacy and tolerance to cimetidine.

Topics: Adolescent; Adult; Aged; Cimetidine; Double-Blind Method; Duodenal Ulcer; Enprostil; Female; Humans; Male; Middle Aged

Enprostil is a new synthetic prostaglandin E2 with antisecretory and mucosal-protective effects. We compared it with ranitidine in the healing of duodenal ulcer and also examined the subsequent relapse rate. Three hundred thirteen patients were recruited in 15 centers in Europe, of whom 158 were treated with enprostil (E) 35 micrograms twice daily and 155 with ranitidine (R) 150 mg twice daily for up to 6 weeks, using a double-blind method. Patients in both groups were of comparable demography. Healing was significantly quicker with ranitidine. Of patients randomized to treatment, healing (intention-to-treat analysis) at 4 weeks was E 47% and R 69%, and at 6 weeks it was E 66% and R 88%. In patients who met all protocol criteria and completed treatment, healing at 4 weeks was E 58% and R 80%, and at 6 weeks it was E 81% and R 92%. Early relief of pain, both during the day and at night, was significantly quicker with ranitidine. Nausea, diarrhea, vomiting, and abdominal pain occurred more often with enprostil. There were no clinically important abnormalities in hematology or biochemistry. Relapse rates were similar. In conclusion, enprostil is not as effective as ranitidine in healing duodenal ulcers.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; Duodenal Ulcer; Enprostil; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Prostaglandins E, Synthetic; Random Allocation; Ranitidine; Recurrence; Time Factors; Wound Healing

The effects of bedtime 70 micrograms and twice daily 35 micrograms doses of enprostil on 24-hour intragastric acidity were investigated in nine duodenal ulcer patients in remission. Median nocturnal acidity decreased significantly by 30% with 35 micrograms twice daily, and by 48% with 70 micrograms at bedtime. In a clinical trial using bedtime dosing, 102 duodenal ulcer patients randomly received either ranitidine 300 mg or enprostil 70 micrograms. More ulcers healed after 4 and 8 weeks treatment with ranitidine than with enprostil (76% ranitidine vs 52% enprostil, at 4 weeks p = 0.0065 and 94% vs 68%, respectively at 8 weeks, P = 0.0007). However, 6 months after cessation of treatment there was no material difference in overall outcome. Despite combining mucosal protection with acid inhibition enprostil treatment conferred no advantage over simple acid inhibition.

Topics: Adult; Aged; Circadian Rhythm; Duodenal Ulcer; Enprostil; Female; Follow-Up Studies; Gastric Acid; Gastric Acidity Determination; Humans; Male; Middle Aged; Ranitidine

One hundred and forty two patients with duodenal ulcer who after a short term study had relief of pain and healed ulcers proved endoscopically were allocated at random to double blind maintenance treatment with enprostil (a synthetic dehydroprostaglandin E2) 35 micrograms or ranitidine 150 mg at bedtime for up to 12 months. Patients were monitored every third month and examined by endoscopy at three, six, and 12 months, or more often if warranted. The cumulative relapse rates in the enprostil group at three, six, and 12 months were 37% (25/67), 56% (37/66), and 62% (41/66), respectively. The corresponding rates in the ranitidine group were 8% (6/71), 19% (13/69), and 29% (20/69). These differences were highly significant and further enhanced by life table analysis adjusting for withdrawals and by an "intention to treat" analysis in which absence of proof of non-recurrence was counted as failure, more patients in the enprostil group having been withdrawn because of adverse events or recorded as non-compliant with the protocol. Enprostil 35 micrograms at bedtime cannot be recommended for preventing relapse of duodenal ulcer. Furthermore, the results challenge the clinical relevance of using so called "cytoprotection" for preventing recurrence.

Topics: Adult; Aged; Antacids; Diarrhea; Double-Blind Method; Duodenal Ulcer; Enprostil; Female; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Random Allocation; Ranitidine; Recurrence; Smoking

The safety and efficacy of enprostil, 35 micrograms twice daily, and of cimetidine, 400 mg twice daily, in the treatment of duodenal ulcers were compared in a randomized, double-blind, parallel, multiclinic study. Endoscopy was performed before treatment and at 2-week intervals for 6 weeks or until the ulcer healed. Patients recorded their drug compliance, antacid use, ulcer symptoms, and adverse experiences daily. One hundred and six patients entered the trial, of which 104 were eligible for the initial endoscopy analysis. Base-line characteristics were similar in the two treatment groups. The cumulative healing rates in the enprostil group were 56%, 86%, and 92% at 2, 4, and 6 weeks, respectively, and those in the cimetidine group were 53%, 84%, and 90% (NS). The healing rates for nonsmokers at 6 weeks were 96% in the enprostil group and 97% in the cimetidine group, which were significantly greater than those for smokers--88% and 81%, respectively. There were no significant differences in the duration, severity, or frequency of daytime or nighttime pain between the groups. Seventeen of the enprostil patients (32%) reported 21 adverse experiences during the trial, and 20 of the cimetidine patients (39%) reported 23 adverse experiences. No patients withdrew because of adverse experiences. The two drugs were similarly safe and effective in the treatment of duodenal ulcer.

Topics: Adolescent; Adult; Aged; Cimetidine; Clinical Trials as Topic; Dinoprostone; Double-Blind Method; Drug Administration Schedule; Duodenal Ulcer; Enprostil; Female; Humans; Male; Middle Aged; Prostaglandins E; Prostaglandins E, Synthetic; Random Allocation

This randomised, double-blind, double-dummy, multiclinic study of duodenal ulcer healing compared the efficacy and safety of enprostil with ranitidine. The six week trial admitted 164 patients with endoscopically demonstrated duodenal ulcer. Ratings of symptoms and adverse events were collated from patients' daily diaries, and endoscopy was repeated to verify healing after four weeks and, if appropriate, after six weeks. Medication used was enprostil (35 micrograms capsule) or ranitidine hydrochloride (150 mg tablet) with matching placebos twice daily. After six weeks, 81% of patients treated with enprostil and 95% of those treated with ranitidine had healed ulcers, a statistically significant difference (p = 0.007). There were no differences between treatment groups for the number of days until the daytime ulcer pain completely ceased. Night-time ulcer pain ceased significantly earlier in the group receiving ranitidine (p = 0.019) and was less severe during the week before the last visit (p = 0.001); daytime pain for ranitidine users was also less severe (p = 0.020) during this week. Mild to moderate adverse experiences were reported by 44% of enprostil and 35% of ranitidine patients. There were no severe adverse events. In conclusion, both enprostil and ranitidine were found to be safe and effective in the treatment of duodenal ulcer. However, the ranitidine regimen used in this trial produced better results than the enprostil regimen.

Topics: Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Duodenoscopy; Enprostil; Female; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Random Allocation; Ranitidine

The effect of 14 days of treatment with enprostil (35 micrograms twice daily) or ranitidine (150 mg twice daily) on platelet function in 21 patients with duodenal ulcer was evaluated in a double-bind, randomized, parallel study. Platelet function, as determined by the results of a coagulation screen, aggregation tests, and an assay for plasma beta-thromboglobulin levels, was assessed before and after 14 days of treatment. No effect on platelet function was observed with either drug in this group of patients.

Topics: Adult; Aged; beta-Thromboglobulin; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Enprostil; Humans; Middle Aged; Platelet Aggregation; Prostaglandins E, Synthetic; Random Allocation

One hundred and eighty patients with endoscopically proved duodenal ulcers were allocated at random to double blind treatment with the synthetic dehydroprostaglandin E2 enprostil 35 micrograms twice daily or ranitidine 150 mg twice daily for up to six weeks. Patients completed the study if ulcer healing and pain relief had occurred at two or four weeks. A total of 163 patients completed the trial. The duration of treatment was longer in the enprostil group (p less than 0.005) and the cumulative healing rates at two, four, and six weeks were 51%, 74%, and 85%, respectively. In the ranitidine group the corresponding figures were 65% (p less than 0.04), 89% (p less than 0.02), and 99% (p less than 0.002). More patients treated with ranitidine reported relief of pain (p less than 0.004 at weeks 5 and 6). The observed superiority of ranitidine 150 mg twice daily over enprostil 35 micrograms twice daily questions the clinical relevance of using so called "cytoprotection" as treatment for duodenal ulcer disease in the short term.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Enprostil; Humans; Middle Aged; Prostaglandins E, Synthetic; Random Allocation; Ranitidine

In a randomized, endoscopically controlled double-blind trial the effectiveness of a twice daily dose of the prostaglandin E2-analogue enprostil was compared with pirenzepine given to 97 ambulatory patients with duodenal ulcers. Under 35 micrograms b.i.d. enprostil the ulcer healing rates after 2, 4 and 6 weeks averaged 41%, 82% and 92%. The corresponding values for pirenzepine were 44%, 72% and 89%. The differences were not statistically significant. Both drugs had a similar influence on the ulcer symptoms.

Topics: Acute Disease; Adult; Anti-Ulcer Agents; Benzodiazepinones; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Enprostil; Female; Humans; Male; Middle Aged; Pirenzepine; Prostaglandins E, Synthetic; Random Allocation; Smoking; Wound Healing

The effect of enprostil, a synthetic dehydro-prostaglandin E2, on meal-stimulated gastric acid secretion and gastrin release was studied in six patients with inactive duodenal ulcer disease. Each subject underwent seven tests in random order on separate days: placebo intragastrically and intraduodenally; enprostil 35 and 70 micrograms both intragastrically and intraduodenally; and ranitidine 150 mg intragastrically. After measuring basal gastric acid secretion and gastrin release, a liquid meal (500 ml, pH 5.5, 40 g protein, 30 g fat, 30 g carbohydrate, 550 Kcal, 768 mOsm) was given. Gastric acid secretion and gastrin release were measured over the next four hours. A second identical meal was instilled and both parameters were measured for an additional four hours. Thirty-five and 70 micrograms of enprostil administered intragastrically reduced total eight-hour gastric acid secretion by 58 percent and 82 percent, respectively (p less than 0.05). The 35 and 70 microgram doses administered intraduodenally decreased gastric acid secretion by 67 percent and 91 percent, respectively (p less than 0.05 compared with placebo). Ranitidine suppressed gastric acid secretion by 95 percent, which was similar to the suppression achieved with the 70 microgram dose of enprostil. The total meal-stimulated integrated gastrin response was significantly suppressed by both intragastric doses of enprostil and by the 70 microgram dose given intraduodenally (p less than 0.05). Compared with placebo, the 35 microgram intragastric and intraduodenal doses decreased the integrated gastrin response by 73 percent and 72 percent, respectively. The 70 microgram intragastric and intraduodenal doses of enprostil reduced the integrated gastrin response by 90 percent and 125 percent, respectively. Ranitidine did not alter the integrated gastrin response. It is concluded that enprostil significantly inhibited both meal-stimulated gastric acid secretion and gastrin release. The response to enprostil occurred in a dose-dependent manner and was similar regardless of the route of administration.

Topics: Duodenal Ulcer; Eating; Enprostil; Fasting; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Ranitidine

Enprostil is a synthetic prostaglandin E2 analogue with gastric anti-secretory, cytoprotective, and gastrin lowering properties. The current multi-center, double-blind, placebo-controlled study was undertaken to evaluate the efficacy and safety of enprostil (35 micrograms twice daily) for the treatment of duodenal ulcers. The study enrolled 87 patients between the ages of 18 and 85 with an endoscopically proved duodenal ulcer between 0.5 and 3.0 cm in its longest dimension and with no other serious medical conditions or abnormal laboratory tests results. Treatment groups were comparable in age, sex, smoking status, ulcer history, and baseline ulcer size. The results indicated that the healing rate for enprostil at two weeks was 38 percent, compared with a placebo rate of 23 percent (p = 0.151). At four weeks, 70 percent of the enprostil-treated patients had healed ulcers, compared with 49 percent of the placebo-treated patients, a statistically significant difference (p = 0.048). Although within the enprostil group the healing rate was higher in nonsmokers (86 percent) than in smokers (58 percent), this difference did not reach statistical significance. Side effects included diarrhea (14 percent) and headache (7 percent). These results indicate that 35 micrograms of enprostil twice daily provides effective and safe therapy for patients with duodenal ulcer.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Enprostil; Humans; Middle Aged; Prostaglandins E, Synthetic; Smoking

Enprostil is a synthetic prostaglandin E2 analogue developed by Syntex. In a randomized, double-blind trial involving 128 patients with duodenal ulcer disease, four weeks of treatment with enprostil at doses of 70 micrograms twice daily and 35 micrograms twice daily produced healing rates (78 percent and 65 percent, respectively) that were statistically significantly higher than the placebo rate (39 percent; p less than 0.05). In a subgroup of smokers, ulcer healing occurred with statistically significantly greater frequency at both the high dose (70 percent) and the low dose (60 percent) when compared with the rate in the placebo group (32 percent; p less than 0.05). The only clinically important side effect was diarrhea, which was generally mild, self-limited, and of short duration. This study demonstrated that enprostil is highly effective in the treatment of duodenal ulcer and has a favorable safety profile.

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

Data were combined for statistical analysis from four European trials comparing enprostil (35 micrograms twice daily) with cimetidine (400 mg twice daily) in the treatment of duodenal ulcer, using a double-blind, randomized design with endoscopic control. A total of 369 patients entered the trials, of whom 348 were eligible for the efficacy analyses and 362 for the safety analyses. Patients were allowed antacids as needed. The pooled cumulative healing rates at two, four, and six weeks were 40, 75, and 84 percent, respectively, for enprostil and 42, 77, and 87 percent, respectively, for cimetidine. There were no significant differences between treatments. Healing rates in both groups were reduced in smokers, in those with larger ulcers at baseline, and in those who reported a higher consumption of alcohol. Age, however, had no effect on healing rates. Digestive system complaints were reported more frequently in the enprostil group, whereas central nervous system complaints were more than twice as frequent in the cimetidine group.

Topics: Adolescent; Adult; Aged; Alcohol Drinking; Belgium; Cimetidine; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Enprostil; Female; France; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Random Allocation; Smoking; Sweden; Time Factors; United Kingdom

This study was designed to compare the effects of enprostil, a synthetic dehydro-prostaglandin E2, on 24-h intragastric pH and serum gastrin profile in patients with duodenal ulcer disease. The dosing regimen included 3 enprostil groups: 35 microgram h.s. (at bedtime), 70 micrograms h.s., and 35 micrograms b.i.d., compared with cimetidine 600 mg b.i.d., and with placebo. Ten patients with inactive duodenal ulcer disease were randomly assigned to all five treatment regimens for 1 wk each according to a Latin Square design. There was a 1-wk washout period between each treatment. Intragastric pH and serum gastrin measurements were carried out on the last day of each treatment week. In placebo-treated patients, intragastric pH rose after each meal and fluctuated between 1.5 and 3.5. Enprostil 35 micrograms b.i.d. and cimetidine elevated pH after breakfast and during the night (p less than 0.05). The single nighttime dose of enprostil had a marked effect on pH only when given in the dose of 70 micrograms and this effect lasted over 13.5 h. The pH values during the night were similar in the groups treated with enprostil 35 micrograms b.i.d. and 70 micrograms h.s. During the daytime, the readings at or above pH 4 were placebo, 5%; cimetidine, 21%; enprostil 35 micrograms b.i.d., 34%. During the nighttime, the readings greater than or equal to 4 were placebo, 12%; cimetidine, 29%; enprostil 35 micrograms b.i.d., 39%; 35 micrograms h.s., 19%, and 70 micrograms h.s., 38%. The postprandial rise in serum gastrin was greatly enhanced by cimetidine, but the change after breakfast was dramatically blunted by enprostil 35 micrograms b.i.d. Gastrin concentration was increased with cimetidine during the night but there was no difference in gastrin concentration overnight between all regimens of enprostil and placebo. This study suggests that (a) enprostil 35 micrograms b.i.d. is as effective as cimetidine 600 mg b.i.d. in suppressing postprandial and nocturnal intragastric acidity; (b) enprostil 35 micrograms b.i.d. and 70 micrograms at night are similarly potent in suppressing nocturnal acidity; and (c) in addition to its cytoprotective effect, enprostil has potent antisecretory and antigastrin properties.

Topics: Adult; Cimetidine; Clinical Trials as Topic; Duodenal Ulcer; Enprostil; Female; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Prostaglandins E, Synthetic; Research Design; Time Factors

Topics: Adolescent; Adult; Biopsy; Drug Evaluation; Duodenal Ulcer; Duodenum; Enprostil; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Parietal Cells, Gastric; Stomach

Topics: Belgium; Duodenal Ulcer; Enprostil; Phenethylamines; Prostaglandins E, Synthetic; Selegiline

A 42-year-old man with a 26-year history of duodenal ulcer volunteered for a 24-hour intragastric pH monitoring study, at which time his fasting gastrin concentration was found to be elevated. Secretin injection decreased the serum gastrin concentration. When not on treatment his total gastrin, gastrin-17 (G-17), and gastrin-34 (G-34) response to a protein-containing breakfast was marked. Immunocytochemical staining of antral biopsies showed hyperplasia of gastrin-containing cells, more pronounced for G-17 than for G-34. Cimetidine or cimetidine plus pirenzepine increased 24-hour intragastric pH, whereas pirenzepine alone rendered the gastric contents more acidic, particularly overnight. The total serum gastrin concentrations increased after meals and were unaffected by cimetidine or pirenzepine; enprostil, however, reduced the postprandial increase in total gastrin, G-34, and G-17. After six weeks of treatment with enprostil, the number of cells containing G-17 and G-34 was reduced. The findings show that G-cell hyperplasia may occur in the presence of a normal fasting serum gastrin concentration; fasting serum gastrin concentrations may fluctuate widely over time; the food-stimulated increase in G-17 was greater than that for G-34, and is associated with more pronounced antral hyperplasia for G-17 and G-34; and enprostil blunts the postprandial increase in G-17, G-34, and total gastrin. These observations suggest that enprostil may reduce G-cell hyperplasia and hypergastrinemia.

Topics: Adult; Cimetidine; Duodenal Ulcer; Enprostil; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Hyperplasia; Male; Pirenzepine; Prostaglandins E, Synthetic; Pyloric Antrum

Topics: Duodenal Ulcer; Enprostil; Humans; Prostaglandins E, Synthetic; Ranitidine

We have studied the effect of a prostaglandin E2 analogue (enprostil), on intragastric acidity, gastric acid and pepsin outputs during a 24 hour period in nine patients with duodenal ulcer in remission. Enprostil 35 micrograms bd dose inhibited 24 hour intragastric acidity by 38% and a 70 micrograms nocturnal dose by 33%. Decrease in nocturnal pepsin secretion was both volume and concentration related.

Topics: Adult; Circadian Rhythm; Duodenal Ulcer; Enprostil; Gastric Acid; Humans; Male; Middle Aged; Pepsin A; Prostaglandins E, Synthetic

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