enprostil and Gastrointestinal-Hemorrhage

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

This study tested the efficacy of enprostil given both at potent antisecretory (35 micrograms twice daily) and weak antisecretory (7 micrograms twice daily) doses in preventing aspirin-induced gastric blood loss measured chemically in gastric washings in 10 volunteers. Aspirin (500 mg four times a day) increased gastric blood loss compared with placebo (p less than 0.001). When enprostil was given in addition to aspirin, gastric blood loss was not significantly different from basal value. The pH of gastric washings was significantly increased by the large but not by the low dose of enprostil compared with placebo. The two doses of enprostil were equally efficacious, suggesting a mucosal protective effect of enprostil independent of acid inhibition.

Topics: Adult; Aspirin; Clinical Trials as Topic; Double-Blind Method; Enprostil; Female; Gastric Acid; Gastrointestinal Hemorrhage; Humans; Hydrogen-Ion Concentration; Male; Prostaglandins E, Synthetic; Random Allocation

Enprostil's ability to protect human gastric mucosa against aspirin-induced damage was investigated in a controlled study. Damage was assessed as blood loss into gastric washings measured spectrophotometrically using orthotolidine in the presence of hydrogen peroxide. Phenol red was used to correct for recovery rates. Five doses of aspirin, 600 mg, given over 48 hours increased blood loss ninefold compared with placebo. Administration of enprostil 35 micrograms twenty minutes before each dose of aspirin halved this blood loss. After enprostil administration, the pH of both aspirated gastric juice and washings was significantly elevated, suggesting that an antisecretory dose had been used. Increased losses of phenol red occurred following both aspirin and enprostil administration, suggesting enhanced gastric emptying or possible absorption of phenol red as a result of aspirin damage. Side effects related mainly to the alimentary system were associated with enprostil treatment. Enprostil reduced aspirin-induced mucosal blood loss but the mechanism is unclear.

Topics: Adult; Aspirin; Capsules; Clinical Trials as Topic; Double-Blind Method; Enprostil; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Hydrogen-Ion Concentration; Male; Prostaglandins E, Synthetic; Research Design; Tablets

A single-blind endoscopic study was undertaken to test the relative efficacy of enprostil, a synthetic analogue of prostaglandin E2, cimetidine, and sucralfate in the prevention of aspirin-induced gastroduodenal mucosal injury. Fifty healthy, non-smoking male volunteers completed the study after having been randomly assigned to receive two weeks of therapy with one of the following regimens: enprostil 35 micrograms twice daily; enprostil 35 micrograms in the morning; cimetidine 200 mg three times daily and 400 mg at night; sucralfate 1 g four times daily; or placebo. In the second week, aspirin (900 mg three times daily) was also administered. Endoscopies were performed before and after the aspirin phase of the study, and lesions (mucosal erosions plus submucosal hemorrhages) were counted in the stomach and duodenal bulb. All treatments were superior to placebo (p less than 0.05). The mean number of lesions in the 70-micrograms enprostil group (8.5) was significantly less than in the 35-micrograms enprostil group, (11.1), the sucralfate group (12.4), or the placebo group (16.0); the benefit over cimetidine (10.1), however, was not statistically significant. The protective effect of enprostil was greatest in the antrum, the site of maximal mucosal injury. Gastrointestinal side effects were reported in all groups, though abdominal pain and dyspepsia were noted more frequently in those taking enprostil.

Topics: Adult; Aluminum; Aspirin; Cimetidine; Clinical Trials as Topic; Duodenum; Enprostil; Gastric Mucosa; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Intestinal Mucosa; Male; Prostaglandins E, Synthetic; Random Allocation; Sucralfate

Prostaglandins protect the gastric mucosa in animals, but the evidence of an effect independent of pH changes in man is not overwhelming. Gastrointestinal bleeding because of non-steroidal anti-inflammatory drugs is a major clinical problem, which we have investigated in a model system measuring bleeding rates caused by short-term administration of aspirin. Of the various strategies tested, only those that elevated intra-gastric pH reduced aspirin-induced bleeding.

Topics: Animals; Anti-Inflammatory Agents; Aspirin; Cattle; Enprostil; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Gastrointestinal Hemorrhage; Humans; Linoleic Acid; Linoleic Acids; Lysine; Male; Milk; Oenothera biennis; Plant Oils; Prostaglandins E, Synthetic; Ranitidine