rioprostil 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

Rioprostil, a synthetic 16-methylprostaglandin E1, combines antisecretory with cytoprotective properties, the latter being active even at doses below those required for acid inhibition. To test whether rioprostil given in antisecretory doses would heal prepyloric ulcers rapidly, we assigned patients with endoscopically proved ulcers randomly to double-blind treatment with 100 micrograms rioprostil twice daily or 150 mg ranitidine twice daily for up to 8 weeks. Recruitment was terminated at the time point of planned interim analysis because the total healing rate was markedly lower than expected. Thirty patients were allocated to each treatment group. The cumulative healing rates at 4 and 8 weeks were 40% and 60%, respectively, in the rioprostil group versus 70% and 90%, respectively, in the ranitidine group (p less than 0.01). Pain relief occurred simultaneously in the two groups. No major adverse effects were noted. These findings question the clinical relevance of using 'cytoprotection' by prostaglandin analogues as treatment for prepyloric ulcer disease in the short term.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Prostaglandins E; Random Allocation; Ranitidine; Rioprostil; Stomach Ulcer

This double-blind trial is undertaken to study the effect of rioprostil on the acid and bicarbonate secretion in patients with gastric ulcer. Pentagastrin stimulation is performed before treatment and 9-20 days after the onset of treatment. In the four patients treated with rioprostil, the bicarbonate secretion increases and the parietal volume secretion decreases (p less than 0.05). The eight patients treated with ranitidine do not show an increase in bicarbonate secretion, but the decrease of the basal acid secretion is more prominent. The index of stimulated bicarbonate secretion/maximal acid output increases by 40% in those who are treated with rioprostil. This may be due to an increase in the cytoprotective activity and to a decrease in the aggressive activity of the gastric juice by rioprostil.

Topics: Adult; Anti-Ulcer Agents; Bicarbonates; Clinical Trials as Topic; Double-Blind Method; Female; Gastric Acid; Humans; Male; Prostaglandins E; Prostaglandins, Synthetic; Ranitidine; Rioprostil; Stomach Ulcer

This study is a multicentre, double-blind, double-dummy, two-way, parallel group comparison of the efficacy and safety of rioprostil and ranitidine in the treatment of active gastric ulcer. Ninety-one patients with gastric ulcer are randomly allocated to treatment with either rioprostil 300 micrograms b.d., or ranitidine, 150 mg b.d. The duration of treatment is 4 weeks, or 8 weeks for the patients who are improved but not healed at 4 weeks. Clinical, endoscopic and laboratory assessments are made before treatment, and after each treatment period. Therapeutic success is defined as complete endoscopic healing of the ulcer. At the end of the treatment period, either 4 or 8 weeks, healing rates are 69% in the rioprostil group, and 66% in the ranitidine group; this difference is not significant (p = 0.86). After the first 4 weeks of treatment the healing rates are 44% and 55% in the rioprostil and ranitidine groups, respectively. The incidence of adverse effects is 22% in the rioprostil group, and 7% in the ranitidine group (p = 0.036). Diarrhoea is the most common side effect (12%), but is usually intermittent and mild. We conclude that rioprostil, 300 micrograms b.d., for up to 8 weeks is as effective as ranitidine, 150 mg b.d., in the treatment of benign gastric ulcer.

Topics: Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Prostaglandins E; Prostaglandins, Synthetic; Randomized Controlled Trials as Topic; Ranitidine; Rioprostil; Stomach Ulcer

The aim of this study is a double-blind evaluation of the efficacy and safety of rioprostil, 300 micrograms, compared with ranitidine, 150 mg, when given twice a day for 4 or 8 weeks in patients with active, uncomplicated gastric ulcer disease. A total of 194 patients are entered into the study, of which 182 are statistically evaluated for efficacy. Eighty-seven receive rioprostil and 95 receive ranitidine. All patients receive two oral doses of study medication daily. After 4 weeks' treatment, 47.1% of the patients receiving rioprostil are endoscopically healed compared with 53.7% of those receiving ranitidine. After 8 weeks' treatment, the cumulative cure rates are 76.2% and 80.9% respectively. Side effects occur in 26% of the patients receiving rioprostil and in 15% of the patients receiving ranitidine. Gastrointestinal side effects are most common. Changes in stool consistency (i.e. soft stools or mild diarrhoea) are the most reported symptoms in patients receiving rioprostil. These effects are generally self-limiting. Three patients on rioprostil and one patient on ranitidine discontinue treatment due to side effects. No clinically significant changes in biochemical variables occur in either group throughout the treatment period. Rioprostil, 300 micrograms b.d., is a safe and effective treatment for gastric ulcer disease. Healing rates and alleviation of pain are comparable for both treatment groups. The change in stool consistency with rioprostil is of only minor clinical importance, that is, it occurs on about 2% of treatment days.

Topics: Anti-Ulcer Agents; Double-Blind Method; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Prostaglandins E; Prostaglandins, Synthetic; Randomized Controlled Trials as Topic; Ranitidine; Rioprostil; 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

Data from a large number of patients (1918) treated with rioprostil, H2-antagonists and placebo, are analysed to examine the safety profile of rioprostil in the treatment of active gastric ulcer or active duodenal ulcer. Rioprostil is administered to 1000 of those patients. Patients who dropped out of the studies and those with adverse drug reactions are classified and compared within different subgroups. The overall dropout rate for rioprostil patients is 8.8%: 2.3% of these because of adverse reactions. The incidence of adverse reactions during rioprostil treatment is 20.9%, with more than 60% of these having gastrointestinal symptoms, mainly appearing in the first week of therapy. Comparisons show a higher incidence of symptoms with rioprostil treatment than with ranitidine treatment because of the gastrointestinal symptoms. Possible differences are found between groups in sex, age, and drug dose. The analysis of laboratory variables does not show clinically important changes as a result of rioprostil treatment.

Topics: Abdominal Pain; Adult; Anti-Ulcer Agents; Diarrhea; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Nausea; Prostaglandins E; Prostaglandins, Synthetic; Rioprostil; Stomach Ulcer

The efficacy and tolerability of the prostaglandin E1 derivative rioprostil (Bay o 6893) was studied in a randomized, double-blind, placebo-controlled trial in 40 patients affected by acute gastric ulcer. At the end of the eight weeks period ulcer healing was achieved in 85% of the rioprostil-treated patients and in 60% of the placebo-treated ones (p less than 0.05). Rioprostil produced a significant reduction of pain and also improved the clinical status. This positive outcome was noted both in smokers and in non-smoking patients, while only this last group improved during the placebo treatment.

Topics: Administration, Oral; Adult; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prostaglandins E; Random Allocation; Rioprostil; Stomach Ulcer

Topics: Adult; Alprostadil; Antacids; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Gastroscopy; Humans; Indomethacin; Misoprostol; Omeprazole; Prostaglandins E; Ranitidine; Rioprostil; Stomach Ulcer

The deleterious effects of acetylsalicylic acid (ASA) on gastric mucosa have been well documented in experimental and clinical studies. With a direct endoscopic assay system we evaluated in healthy volunteers whether pretreatment with prostaglandin analogues (misoprostol, rioprostil), omeprazole and ranitidine prevented ASA-induced gastric mucosal injuries. Ranitidine (2 X 150 mg/d) in large antisecretory doses almost completely abolished these changes (p less than 0.05). By contrast, misoprostol (4 X 50 micrograms/d and 4 X 200 micrograms/d), rioprostil (3 X 100 micrograms/d), omeprazole (5 mg and 10 mg/d) as well as ranitidine in non-antisecretory doses (2 X 25 mg/d) did not reduce gastric mucosal injury after single-dose ASA administration. The results of this trial indicate that socalled cytoprotective doses of prostaglandins, omeprazole and ranitidine in contrast to animal findings are not effective in preventing acute ASA-induced mucosal damage.

Topics: Adult; Alprostadil; Anti-Ulcer Agents; Aspirin; Benzimidazoles; Clinical Trials as Topic; Double-Blind Method; Gastric Mucosa; Gastroscopy; Humans; Misoprostol; Omeprazole; Prostaglandins E; Prostaglandins, Synthetic; Random Allocation; Ranitidine; Rioprostil; Stomach Ulcer

The antiulcer activity of BAY P 14551 a thiazolylaminobenzimidazole derivative, was evaluated in different experimental ulcer models and its antiulcer activity was compared to that of different reference drugs. The overall activity of the compound was equal to or more potent than that of reference antiulcer drugs, such as pirenzepine, cimetidine and carbenoxolone, but it was not as potent as rioprostil. The ED50 values (expressed as mumol/kg p.o.) were 68 (confidence limits: 51-91) for indomethacin-induced ulcers, 21 (confidence limits: 13-31) for stress-induced ulcers and 1260 mumol/kg p.o. (confidence limits: 412-3800) for ulcers induced by absolute ethanol. The compound had no activity against cysteamine-induced duodenal ulcers and lost its cytoprotective activity in adrenalectomised rats. Since inhibition of gastric acid secretion was seen, if at all, only with the higher doses, the gastro-protective action of BAY P 1455 seemed not to be due to an antisecretory effect, but more likely to a gastroprotective action as hypothesised for prostaglandins.

Topics: Adrenalectomy; Animals; Anti-Ulcer Agents; Benzimidazoles; Cimetidine; Corticosterone; Cysteamine; Duodenal Ulcer; Ethanol; Female; Gastric Acid; Immersion; In Vitro Techniques; Indomethacin; Male; Pirenzepine; Prostaglandins E; Pylorus; Rats; Rats, Inbred Strains; Rioprostil; Stomach Ulcer; Stress, Psychological; Thiazoles

The present study investigated the preventive and curative effects of prostaglandins (PGs) on gastric ulcer in rats induced by physical or psychological stresses; some rats were electrically shocked, while others were exposed to affective stimuli arising from the shocked animals. The synthetic PGs dimethyl-PGE2 and rioprostil were administered orally, and their preventive effect on gastric ulceration was evaluated by determining the incidence and the ulcer index of lesions. The curative effect of drugs on ulcer healing was evaluated by determining a time-dependent change in the mucosal surface of the stomach with an endoscopic technique. Oral administration of dimethyl-PGE2 or rioprostil (25 and 50 micrograms/kg) prevented gastric ulceration significantly. Oral administration of these drugs (50 micrograms/kg, twice per day) significantly promoted the healing process of lesions 24 and 36 hr after termination of stress loading. The present results give direct evidence of the curative effect of PGs on stress ulcers and suggest that application of the endoscopic technique to the pathology of the rat's stomach may be a substantial aid in the preclinical evaluation of antiulcer drugs.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Anti-Ulcer Agents; Electroshock; Gastric Mucosa; Gastroscopy; Male; Prostaglandins E; Prostaglandins E, Synthetic; Rats; Rioprostil; Stomach Ulcer; Stress, Physiological; Stress, Psychological

Rioprostil, a primary alcohol prostaglandin E1 analog, inhibits gastric acid secretion and prevents gastric lesions induced by a variety of irritants in experimental animals. Because rioprostil is relatively short-acting, it would be of significant benefit clinically if its duration of action could be extended to allow once daily dosing. This investigation demonstrates that when administered via an osmotically driven pump (Osmet, Alza Corp.), rioprostil prevents the acute effects of aspirin on the gastric mucosa of dogs, accelerates the healing of aspirin-induced gastric lesions, and heals preexisting aspirin-induced gastric lesions during chronic administration of aspiring. The potency of rioprostil against acute gastric lesion formation was greatest when delivered from a 24-hr release pump (ED50 = 0.77 micrograms/kg/24 hr) and was 37 times greater than when administered as a single oral bolus. In addition, this activity occurred at doses which had little or no gastric antisecretory activity in betazole-stimulated Heidenhain pouch dogs. When delivered from a 24-hr pump, rioprostil (100 micrograms/kg/24 hr) healed preexisting aspirin-induced gastric lesions within 8 days after removal of aspirin, or after 15 days during continued daily aspirin administration. Additional studies determined that administration of rioprostil at doses of 720, 1440, or 2160 micrograms/kg/24 hr (935-2805 times the gastroprotective ED50 in 24 hr pumps) was well tolerated, with only slight, transient increases in body temperature, softening of the stools, and mild sedation at the highest dose. Administration of rioprostil daily for 5 days at 960 micrograms/kg/24 hr from 24-hr release pumps was also well tolerated by all dogs with no evidence of any accumulation of effect of rioprostil. In summary, administration of rioprostil via an osmotic pump increases its potency and duration of action against the gastric lesion-inducing effect of aspirin, and maintains a wide ratio of safety.

Topics: Acute Disease; Administration, Oral; Animals; Anti-Ulcer Agents; Aspirin; Chronic Disease; Dogs; Female; Gastric Juice; Infusion Pumps; Male; Prostaglandins E; Rioprostil; Stomach Ulcer

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Humans; Peptic Ulcer; Prostaglandins E; Prostaglandins, Synthetic; Rioprostil; Stomach Ulcer

It is well known that nonsteroidal antiinflammatory agents produce gastric mucosal lesions in both laboratory animals and man. However, the effect of an arthritic condition on their susceptibility to ulcerogenic agents and on the efficacy of antiulcer agents is less definitive. As a model to explore these questions, the effect of oral administration of aspirin or ethanol on gastric lesion formation was examined in rats with or without established adjuvant-induced polyarthritis. In addition, the antilesion efficacy of rioprostil, a primary alcohol prostaglandin E1 analog, was evaluated in both groups of rats. The results demonstrated that arthritic rats were more sensitive to the lesion-inducing effect of aspirin, but were more resistant to the lesion-inducing effect of ethanol when compared to normal rats. An increase in endogenous gastric prostaglandin production in arthritic rats may account for their relative resistance to ethanol. Aspirin inhibited the prostaglandin synthetic capacity of the stomach in both normal and arthritic rats, which may be responsible for eliminating the relative resistance of arthritic rats to gastric irritation. Rioprostil effectively prevented aspirin or ethanol-induced lesion formation in both arthritic and nonarthritic rats, but its potency against either irritant was decreased in arthritic rats.

Topics: Animals; Anti-Ulcer Agents; Arthritis; Arthritis, Experimental; Aspirin; Ethanol; Male; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains; Rioprostil; Stomach Ulcer

Rioprostil, a primary alcohol prostaglandin E1 analog, is currently undergoing clinical evaluation for use in the treatment of peptic ulcer disease. Since antacids are often used in conjunction with other antiulcer agents, studies were conducted to determine if concomitantly administered antacid modifies the antiulcer activity of rioprostil. This investigation showed that concomitant administration of antacid (0.25-1.0 ml Maalox) does not inhibit the ability of rioprostil (0.125-4.0 micrograms/kg, p.o.) to prevent ethanol-induced gastric lesions in rats. The antiulcer effect of the drug combination was additive, suggesting that each compound acts independently to prevent gastric bleeding. These results in animals suggest that clinically the use of antacid will not compromise the efficacy of rioprostil and that the combination may be a useful mode of therapy for the treatment of peptic ulcer disease.

Topics: Alprostadil; Animals; Antacids; Anti-Ulcer Agents; Gastric Mucosa; Male; Prostaglandins E; Rats; Rioprostil; Stomach Ulcer

Gastrointestinal irritation is the most significant side effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAID) for treatment of arthritic conditions. Rioprostil, a primary alcohol prostaglandin E1 analog, prevents gastric bleeding induced by several NSAID in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of rioprostil (50 micrograms/kg BID for 15 days) did not influence the course of the adjuvant disease in rats or alter the antiinflammatory or analgesic effect of the NSAID. In a 13 week efficacy study in dogs, rioprostil (40-60 micrograms/kg, PO) completely prevented gastric hemorrhagic lesions induced by daily administration of aspirin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis; Arthritis, Experimental; Disease Models, Animal; Dogs; Gastric Mucosa; Male; Peptic Ulcer Hemorrhage; Prostaglandins E; Pylorus; Rats; Rats, Inbred Lew; Rats, Inbred Strains; Rioprostil; Stomach Ulcer

Rioprostil (2-decarboxy-2-hydroxymethyl-15-deoxy-16RS-hydroxy-16-methyl prostaglandin (PG)E1) is a potent orally active inhibitor of gastric acid secretion in both rats and dogs. It prevents gastric lesions in rats induced by ethanol, acetylsalicylic acid, strong acid, strong base, hypertonic saline and thermal injury at doses 100 times less than its antisecretory dose. The cytoprotective effect of rioprostil can be observed when given 4 min before challenge with ethanol and measured 60 min later. The peak antiulcer effect is observed when rioprostil is given 30 min before ethanol challenge and the oral ED50 is 1.93 (1.74-2.15) micrograms/kg. Rioprostil possesses weak PGE-like activity in an isolated tissue cascade, no contragestational activity in rats, hamsters or rabbits, and no remarkable cardiovascular or pulmonary activity in dogs. The animal pharmacology of this compound suggests that it should be useful in the treatment or prophylaxis of peptic ulcer disease and gastric lesions associated with noxious irritants such as ethanol and nonsteroidal antiinflammatory drugs.

Topics: Animals; Anti-Ulcer Agents; Cricetinae; Dogs; Ethanol; Female; Gastric Acid; Gastric Mucosa; Hemodynamics; Lung; Male; Prostaglandins E; Rabbits; Rats; Rioprostil; Species Specificity; Stomach Ulcer; Time Factors