triletide and Stomach-Ulcer

A study was carried out in 30 out-patients with endoscopically confirmed active, benign gastric or duodenal ulceration to assess the comparative effectiveness and tolerance of treatment with triletide, a new synthetic tripeptide with anti-ulcer properties, with that of conventional antacids. Patients were allocated at random to receive treatment with either 1.6 g aluminium hydroxide and 1.6 g magnesium hydroxide per day or the antacids plus 1.5 g triletide per day over a period of 8 weeks. Heartburn and epigastric pain, monitored every other week, were significantly relieved by both treatments, but to a significantly greater extent (70% vs 20% on average, p less than 0.01) and significantly faster (p less than 0.01) in the presence of triletide. Endoscopic control showed that the patients who had triletide experienced complete healing in a significantly greater proportion (73% vs 27%, p less than 0.02) than those who had antacids only. The efficacy of treatments was the same, regardless of the actual ulcer location. Routine haematology and haematochemistry findings were unaffected by either treatment, and subjective possible side-reactions were limited to constipation (9 complaints overall) which is a well-known side-effect of antacid treatment. It would appear, therefore, that triletide is at least as well tolerated as antacids, while promoting the healing of peptic ulcers in a significantly greater proportion of patients and easing symptoms significantly faster and to a greater extent than antacids alone, regardless of the ulcer location.

Topics: Adult; Antacids; Anti-Ulcer Agents; Clinical Trials as Topic; Drug Tolerance; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Oligopeptides; Random Allocation; Stomach Ulcer; Time Factors

Two parallel groups, each of 10 out-patients with endoscopically confirmed benign gastric ulcer, were randomly assigned to receive either 1.5 g/day of triletide, a new tripeptide shown to increase the synthesis of gastroduodenal mucus and to antagonize thromboxane A2, or 0.3 g/day of carbenoxolone. Both drugs were given orally in 3 divided doses for 4 weeks, according to the controlled design. Endoscopy showed that a greater proportion of patients treated with triletide benefited from treatment (60%) in comparison with those who had carbenoxolone (40%), but the difference was not significant. Weekly monitoring of epigastric pain, heartburn and antacid intake showed both treatments to be effective, and triletide to be overall faster acting (p less than 0.01 for epigastric pain). Subjective complaints of possible side-reactions were not recorded with either treatment; routine physical examination, haematology and haematochemistry remained unaffected by triletide, whereas treatment with carbenoxolone was associated with a significant increase in both systolic and diastolic blood pressure and with a significant decrease (p less than 0.05) in blood potassium levels. Triletide, therefore, appeared to be an effective and well-tolerated means for the therapy of gastric ulcer, and by virtue of its significantly greater symptomatic action and greater tolerance in comparison with a standard cytoprotective treatment such as carbenoxolone, it is suggested that triletide deserves consideration in the management of peptic ulcer.

Topics: Adult; Antacids; Anti-Ulcer Agents; Carbenoxolone; Clinical Trials as Topic; Female; Glycyrrhetinic Acid; Humans; Male; Middle Aged; Oligopeptides; Random Allocation; Stomach Ulcer; Time Factors

Three groups of 15 patients with endoscopically confirmed active gastric or duodenal ulcer were treated over a period of 8 weeks with daily doses of 1, 1.5 or 2 g triletide, an anti-ulcer agent which acts by enhancing the mucosal defence capacity. Intensity of epigastric pain and of heartburn and weekly consumption of standard antacid tablets, as well as possible accessory symptoms, were recorded every other week, endoscopy was repeated at the end of treatment and routine haematology and haematochemistry performed before and after treatment. The proportion of patients found to be endoscopically healed was significantly correlated to the log of the dose used, giving an ED50, under the test conditions, of 1.2 g/day (86.7% healed at 2 g/day). The improvement in each assessed symptom was significantly correlated with time according to an exponential regression. The computed exponent indicated that each higher dose resulted in a significantly faster regression of symptoms than each lower dose (mean time to decrease symptoms by 50%; 4.3 weeks at 2 g/day; 7.4 weeks at 1.5 g/day; and 20.8 weeks at 1 g/day). Moreover, two-ways analysis of variance indicated a significant dose-time interaction (p less than 0.01); thus, the improvement provided at any given time was more than proportional to the used dose. Tolerance was good at all three dose levels and no variations in haematology and haematochemistry could be detected. It is concluded that triletide, at a dose of between 1.5 and 2 g/day according to the patient's condition, appears to be an effective and well-tolerated means of promoting healing and controlling symptoms in peptic ulcer patients.

Topics: Adult; Aged; Antacids; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Oligopeptides; Stomach Ulcer; Time Factors

A study was carried out in 15 patients with gastric or duodenal ulcer to assess whether the efficacy of the antisecretory agent cimetidine might be improved by the addition of a cyto-protective agent, triletide, to the treatment regimen. The patients were treated for an average of 11 +/- 5 days with 0.2 g parenteral cimetidine per day plus 1.5 g oral triletide per day. Endoscopy was performed before and after treatment, as well as routine haematology and haematochemistry. Intensity of symptoms and signs of the illness was scored and recorded daily during the first 5 days of treatment, as well as the extent of antacid intake. Collected data were compared with those of a series of 15 superimposable patients who had shortly before been treated with 0.2 g/day of cimetidine alone. A greater proportion of patients given the combination was found to be endoscopically healed after treatment in comparison with those who had cimetidine alone (53% vs 40%). Intensity of symptoms decreased significantly faster and to a significantly greater extent in the same patients, as did antacid intake. The intensity of objective signs (tenderness, melaena) showed a similar but not significantly different trend. Total symptom intensity decreased twice as fast with the combination in comparison with cimetidine alone (time to decrease by 50%: 4.2 days vs 8.2, respectively). There was no evidence of side-effects or intolerance during treatment.

Topics: Adult; Aged; Anti-Ulcer Agents; Cimetidine; Drug Therapy, Combination; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Oligopeptides; Retrospective Studies; Stomach Ulcer; Time Factors

There is accumulating evidence that the presence of the imidazole ring is essential for the inhibition of the thromboxane synthetase activity of several compounds synthetized so far. Inhibition of arachidonic acid (AA) induced platelet aggregation was observed by us with a series of tripeptides in which the imidazole ring belongs to histidine, included in a proper aminoacid sequence. Among these compounds the N-acetyl-L-phenylalanyl-L-phenylalanyl-L-histidine methylester (ZAMI-420) was the most effective. The bioassay of the supernatant of an AA-added platelet-rich plasma (PRP) preparation, preincubated with increasing concentrations of ZAMI-420, showed a dose-related reduction in thromboxane-A2 (TXA2)-like activity, an increase of PG-like response and disappearance of the TXB2 peak in the radiochromatogram; RIA experiments led to the same results. ZAMI-420 does not influence cyclooxygenase activity as the AA-induced increase in O2-consumption by the microsomal fraction of bovine seminal vesicles was unaltered by this compound. Administered orally to the rat, ZAMI-420 was able to prevent gastric damage provoked by a variety of pharmacological agents, including ASA, 5HT and alcohol. The protective effect on experimentally-induced gastric damage is not mediated through the antisecretory properties of this compound but is more likely to be due to a cytoprotective mechanism based on blockade of TXA2 synthesis.

Topics: Animals; Arachidonic Acids; Biological Assay; Carbenoxolone; Chromatography, Thin Layer; Cimetidine; Ethanol; Female; Guinea Pigs; Imidazoles; Oligopeptides; Platelet Aggregation; Prostaglandin-Endoperoxide Synthases; Rabbits; Radioimmunoassay; Rats; Rats, Inbred Strains; Serotonin; Stomach; Stomach Ulcer; Thromboxane A2; Thromboxanes; Vasoconstriction