arbaprostil and Stomach-Ulcer

Three randomized, placebo-controlled multiclinic trials involving arbaprostil dosages of (a) 10 micrograms; (b) 25 micrograms; and (c) 10, 25, or 50 micrograms orally for 4 wk in patients older than 18 yr with rheumatoid arthritis or osteoarthritis who had endoscopically documented nonsteroidal antiinflammatory drug-associated gastric mucosal damage were conducted in the United States. All patients continued taking the nonsteroidal antiinflammatory drugs and were reendoscoped after 4 wk of therapy. Success at that time was defined as complete resolution of all gastric mucosal damage. Six hundred fifty-eight patients were enrolled in the three trials. Significantly more patients experienced healing in the arbaprostil treatment groups in all trials compared with those who received placebo. The healing rates in the various trials were 68% and 32% (10 micrograms vs. placebo; p = 0.007); 77% and 23% (25 micrograms vs. placebo; p less than 0.001); and 52%, 46%, 35%, and 16% (50, 25, and 10 micrograms vs. placebo; p less than 0.001, less than 0.001, and 0.002, respectively). Diarrhea, mostly of a mild nature, was the only arbaprostil-associated side effect and was found with the 25- and 50-microgram dosages (33% and 59%, respectively). No exacerbation of arthritis signs or symptoms was found. Arbaprostil at doses with varying effects on gastric acid secretion (25 and 50 micrograms) was documented in these trials to be an effective and safe agent for healing gastric mucosal damage associated with aspirin or other nonsteroidal antiinflammatory drugs in patients with either rheumatoid arthritis or osteoarthritis without adversely affecting joint symptomatology.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Aluminum Hydroxide; Anti-Inflammatory Agents, Non-Steroidal; Arbaprostil; Arthritis, Rheumatoid; Aspirin; Female; Gastric Mucosa; Humans; Male; Middle Aged; Multicenter Studies as Topic; Osteoarthritis; Placebos; Prostaglandins E, Synthetic; Randomized Controlled Trials as Topic; Stomach Diseases; Stomach Ulcer

A randomized, double-blind, placebo-controlled, multiclinic trial evaluated arbaprostil [15(R)-15 methyl prostaglandin E2] for the treatment of acute gastric ulcer, achieving an overall enrollment of 124 patients (of which 113 were considered evaluable). This 6-wk trial used an arbaprostil dose of 10 micrograms q.i.d., which has little gastric acid antisecretory activity. Endoscopies were performed after 21 and 42 days of treatment, at which times the arbaprostil and placebo healing rates, respectively, were 6/59 (10.2%) and 4/53 (7.6%) on day 21 and 25/59 (42.4%) and 16/50 (32.0%) on day 42. No significant differences between the treatment groups were found for pain relief, antacid consumption, and mucosal healing. This trial documents that a 10-micrograms dose of arbaprostil (which may be considered cytoprotective because of its small effect on gastric acid secretion), although safe and associated with no side effects, is not efficacious in healing acute gastric ulcers.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Arbaprostil; Clinical Trials as Topic; Double-Blind Method; Female; Gastric Mucosa; Humans; Male; Middle Aged; Multicenter Studies as Topic; Prostaglandins E, Synthetic; Random Allocation; Stomach Ulcer

Twenty outpatients with an endoscopic diagnosis of gastric ulcer were evaluated for 6 wk in a randomized, double-blind trial comparing 15(R)-15-methyl prostaglandin E2 (Arbacet) (10 micrograms, 0.5 h before each meal and at bedtime) with placebo. Endoscopy was performed at 3 wk and 6 wk during the study period. Five of nine patients (56%) taking Arbacet and seven of 11 patients (64%) in the placebo group had complete healing of their gastric ulcer. Healing occurred in four patients from the Arbacet group and three patients in the placebo group at 3 wk. A cytoprotective dose of Arbacet (40 micrograms daily) is not significantly better than placebo in healing gastric ulcers.

Topics: Acute Disease; Arbaprostil; Clinical Trials as Topic; Double-Blind Method; Female; Gastroscopy; Humans; Male; Middle Aged; Placebos; Prostaglandins E, Synthetic; Random Allocation; Stomach Ulcer

The effects of dl-(15R)-15 methyl-PGE2 methyl ester (PG6E), in experimental ulcers induced by absolute alcohol, HCl, indomethacin, pyloric ligation and chronic acetic acid in rats were studied. PG6E at doses 10-80 micrograms.kg-1 was shown to have significant protective effect. PG6E (30-60 micrograms.kg-1) was also found to reduce markedly the acid secretion, pepsin activity, DNA content of the juice collected from pylorus ligated stomach of rats and increase markedly the content of gastric mucosa hexosamine in mice given PG6E (30-60 micrograms.kg-1 po for 3 d). At doses of 40-80 micrograms.kg-1, PG6E was able to have no significant effect on gastric emptying time in rats and gastrointestinal tract movement in mice. It appears that PG6E was shown to inhibit the aggressive factors and increase the protective factors of gastric mucosa. This may hopefully become a new antiulcer agent.

Topics: Animals; Anti-Ulcer Agents; Arbaprostil; Female; Gastric Acid; Gastric Emptying; Gastrointestinal Motility; Male; Mice; Rats; Rats, Wistar; Stomach Ulcer

The effects of arbaprostil (CU-83), a newly synthesized prostaglandin (PG) E2 analogue, on gastric lesions were investigated. Experiment 1: The animals were divided into 3 groups: 1. the control group: untreated, 2. 50% ethanol group: rats were given 1 ml of 50% ethanol intragastrically, and 3. arbaprostil + 50% ethanol group: arbaprostil (10 micrograms/kg) was administered p.o. 30 min before 50% ethanol administration. 1 h after ethanol administration, stomachs were isolated, and gastric mucosal lesions were observed. Experiment 2: Rats were divided into 4 groups; 1. the control group; untreated, 2. 6 h stress group; animals were placed in a stress cage and immersed into a water bath (23 degrees C) for 6 h, 3. arbaprostil (10 micrograms/kg) + 6 h stress group, and 4. arbaprostil (100 micrograms/kg) + 6 h stress group; arbaprostil 10 micrograms/kg or 100 micrograms/kg was administered 30 min before 6 h of water immersion stress, respectively. In each experiment, stomachs were isolated and gastric mucosal lesions were observed. Immediately after the observation of lesions, the fundic mucosal layer was separated from the muscle layer, and mucosal PGs levels were measured by high performance liquid chromatography. Four kinds of PGs, i.e., 6-keto-PG F1 alpha, PGF2 alpha, PGE2, and PGD2 were detected in gastric mucosa. Administration of 50% ethanol and water immersion stress induced gastric lesions and decreased all 4 mucosal PGs levels. Arbaprostil, 10 micrograms/kg, reduced ethanol-induced gastric lesions and maintained mucosal PGs levels, concomitantly, however, the same doses of arbaprostil did not show a protective effect against water immersion stress-induced gastric lesions or decreases in PGs levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arbaprostil; Chromatography, High Pressure Liquid; Ethanol; Immersion; Male; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Psychological

The efficacy of sucralfate, 15(R)15-methyl prostaglandin E2, and cimetidine in protecting against ethanol injury in rat stomachs was examined. Rats that had been fasted were pretreated intragastrically with either sucralfate 160 mg/kg, 15(R)15-methyl prostaglandin E2 16 micrograms/kg, cimetidine 100 mg/kg, or an equal amount of vehicle alone (control). One hour later, all rats received 1 ml of 99.5 percent ethanol orally and were killed 15 minutes or 24 hours later. Stomachs were removed, and mucosal damage was assessed macroscopically as well as by scanning electron microscopy. Pretreatment with either 15(R)15-methyl prostaglandin E2 or sucralfate significantly reduced the number and extent of ethanol-induced mucosal gastric lesions; pretreatment with cimetidine, however, failed to produce positive results. It is concluded that the abilities of 15(R)15-methyl prostaglandin E2 and sucralfate in protecting against ethanol injury are comparable.

Topics: Animals; Arbaprostil; Basement Membrane; Cimetidine; Drug Interactions; Epithelium; Ethanol; Gastric Mucosa; Gastrointestinal Hemorrhage; Male; Microscopy, Electron, Scanning; Prostaglandins E, Synthetic; Rats; Stomach Ulcer; Sucralfate

We studied the effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various acute and chronic gastric lesions produced in rats. Arbaprostil significantly inhibited gastric secretion in 4 hr-pylorus-ligated preparations when given intraduodenally in a dose of 30 or 100 micrograms/kg. The agent, however, significantly stimulated gastric secretion of rats with either a ligated or intact pylorus when given orally in doses of 3-100 micrograms/kg. Orally administered arbaprostil dose-dependently prevented the development of HCI-ethanol-, histamine-, water-immersion stress-, or indomethacin-induced gastric erosions. Intraduodenally administered arbaprostil also dose-dependently prevented the development of aspirin-induced gastric erosions in pylorus-ligated rats. Arbaprostil, given orally in doses of 1-100 micrograms/kg twice daily for 2 weeks, had little or no effect on the healing of acetic acid-induced gastric ulcers. However, oral administration of the agent in a dose of 3 or 10 micrograms/kg twice daily for 4 weeks significantly accelerated the healing of acetic acid-induced gastric ulcers. The increase in doses up to 100 micrograms/kg twice daily for 4 weeks had no effect on ulcer healing. These results indicate that arbaprostil, at either antisecretory or even acid stimulating doses, is effective in preventing the development of acute gastric erosions and in accelerating the healing of chronic gastric ulcers.

Topics: Acetates; Acetic Acid; Administration, Oral; Animals; Arbaprostil; Aspirin; Dose-Response Relationship, Drug; Gastric Acid; Gastric Mucosa; Male; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Stomach Ulcer

Topics: Arbaprostil; Atrial Natriuretic Factor; Humans; Peptic Ulcer Hemorrhage; Prostaglandins E, Synthetic; Stomach Ulcer

The effect of 15(R)-15 methyl PGE2 on the evolution of gastric ulcers induced by endoscopic Nd:YAG laser photocoagulation was studied. By continuous application of 50 to 70 watt power for 4 sec at a distance of 15 mm from the gastric mucosa, reproducible ulcers can be induced. The effect of the drug in nonantisecretory doses (10 micrograms/kg) on the acute ulcer formation and on the healing rate was evaluated in mongrel dogs by light microscopy. Local administration or oral pretreatment did not influence the size or depth of acute ulcers (7.4 mm in diameter) as compared to a control series (7.2 mm). Pretreatment for several days, however, had a marked beneficial effect on the healing rate of the ulcers (1.71 mm after 7 days compared to 2.76 mm for the control series). From these data it may be concluded that 15(R)-15 methyl PGE2 has a beneficial effect on ulcer healing, even in nonantisecretory doses.

Topics: Administration, Oral; Animals; Arbaprostil; Dogs; Lasers; Prostaglandins E, Synthetic; Stomach Ulcer

Topics: Adolescent; Arbaprostil; Coagulants; Female; Humans; Peptic Ulcer Hemorrhage; Prostaglandins E, Synthetic; Stomach Ulcer; Stress, Physiological