Alosetron does not affect the visceral perception of gastric distension in healthy subjects.

BACKGROUND: The effect of alosetron, a new specific 5-HT3 receptor antagonist, on the visceral perception in response to gastric distension was assessed in 12 healthy male subjects in a randomized, double-blind, placebo controlled crossover trial. METHODS: Each subject was given orally either alosetron 1 mg b.d. or placebo b.d. for 6 days (wash-out period 7-28 days). At the end of each dosing period, both isobarometric and isovolumetric gastric distensions were performed using an electronic barostat. RESULTS: Alosetron did not modify the gastric wall compliance (pressure-volume relationship). Alosetron had an effect similar to placebo on the visceral perception scores in both isobarometric and isovolumetric distensions. The mean (+/- SEM) thresholds for abdominal discomfort were, respectively, 16.8 +/- 0.7 mmHg and 825 +/- 61 mL with alosetron, 16.7 +/- 0.6 mmHg and 883 +/- 45 mL with Placebo (P = NS). CONCLUSIONS: 5-HT3 receptors do not appear to be involved in the visceral perception of gastric distension in healthy subjects.

[Comparative efficacy of omeprazole and cimetidine in the treatment of duodenal ulcer in the acute stage. A French multicenter, controlled therapeutic trial]. / Efficacité comparée de l'oméprazole et de la cimétidine dans le traitement de l'ulcère duodénal en poussée évolutive. Essai thérapeutique, contrôle multicentrique français.

Omeprazole is a proton pump inhibitor which induces a dose-dependent reduction of gastric acid secretion. To assess its efficacy in healing and alleviating the symptoms of duodenal ulcer, a randomized and double-blind study was conducted in 26 French centers comparing omeprazole 20 mg o.m. with cimetidine 400 mg b.i.d. After two weeks' treatment (285 cases), healing, assessed by endoscopy, was obtained in 64.5 p. 100 of omeprazole-treated patients, and in 44.3 p. 100 of cimetidine-treated patients (p = 0.0008). After 4 weeks treatment (232 cases), 90.1 p. 100 of omeprazole-treated patients healed, compared to 79.3 p. 100 of cimetidine-treated patients (p = 0.03). After 2 weeks treatment, there was no difference between the groups as far as nocturnal pain was concerned; however there was a significant difference in favor of omeprazole in the resolution of mild or moderate day-time pain (p = 0.01). There were no clinical or biochemical adverse events which could be ascribed to either of the treatments tested.

[Omeprazole (20 mg daily) compared to ranitidine (150 mg twice daily) in the treatment of esophagitis caused by reflux. Results of a double-blind randomized multicenter trial in France and Belgium]. / Oméprazole (20 mg/j) comparé à ranitidine (150 mg 2 fois/j) dans le traitement de l'oesophagite par reflux. Résultats d'un essai multicentrique franco-belge, randomisé en double insu.

We report the results of a trial of omeprazole 20 mg daily versus ranitidine 150 mg b.i.d. in the short-term management of erosive or ulcerative esophagitis. The principal aim of the trial was to assess the healing rates of the esophageal lesions. The trial was conducted in 19 centers (16 in France and 3 in Belgium). The lesions of the esophageal mucosa were defined as follows: grade 2 (n = 112), round or linear erosions; grade 3 (n = 33), confluent erosions affecting the total esophageal circumference; or grade 4 (n = 11), erosions as described above plus deep ulcerations or peptic stenosis which did not need endoscopic dilatation. The main criterion was the complete healing of esophageal lesions after 4 weeks of treatment. Patients were randomly allocated to double-blind treatment with omeprazole or ranitidine. Clinical and endoscopic examinations were done on inclusion in the trial and at day 29 +/- 6, and again at day 57 +/- 6 if esophagitis was unhealed. No patient was excluded from the analysis on an "intention-to-treat" basis, and 25 patients were excluded from the "per protocol" analysis, mainly because of poor compliance with the trial protocol. The healing rate at weak 4 was 50 of 62 patients (81 p. 100) treated with omeprazole and 31 of 69 patients (45 p. 100) with ranitidine (p less than 0.001). The corresponding figures at week 8 were 58 of 61 (95 p. 100) and 40 of 61 (65 p. 100) (p less than 0.001).

Low dose omeprazole effects on gastric acid secretion in normal man.

The pharmacological effects of low dose of omeprazole (Om) are not well known. This prompted us to investigate the effects of a 7-day treatment with a low dose of Om, 10 mg/d (Om10), on gastric acid secretion and serum gastrin levels and to compare the results with those obtained with an effective antisecretory dose of 20 mg/d (Om20). Twelve healthy volunteers received randomly and double-blind for three periods of 7 days, separated by at least 7 days, one capsule of placebo (P), Om10, Om20, given daily in the morning, in fasting condition. The last day of each period, 24 h pH was recorded using a glass electrode connected to a Digitrapper (Synectics). At the end of each pH-metry, acid secretion was measured in basal conditions (BAO), after sham-feeding (SAO) and after i.m. injection of 6 micrograms X kg-1 of pentagastrin (PAO). Whatever the threshold pH chosen, there was a statistically significant difference between P and Om10, P and Om20, and Om10 and Om20. Inhibition of acid concentrations was dose-dependent and prolonged, including nocturnal time. However, when considered on an individual basis, five subjects did not respond to Om10. More than 24 h after the last dose of Om has been administered, BAO, SAO and PAO were significantly reduced by either Om10 (respectively -52, -35 and -28 p. cent) and Om20 (respectively -60, -58 and -50 p. cent). Fasting serum gastrin concentration was significantly increased after Om20 treatment but not after Om10. We conclude that treatment with Om10 has a consistent and long lasting inhibitory action on gastric acidity without statistically significant effect on serum gastrin levels. These results suggest that 10 mg Om daily should be sufficient in some duodenal ulcer patients to effectively inhibit gastric acidity specially when long-term treatment seems to be indicated.

[Radiotelemetric study of the effects of antacids and cimetidine on intragastric pH (author's transl)]. / Etude par radio-télémétrie de l'effet sur le pH gastrique de médicaments anti-acides de contact et de la cimétidine.

Radiotelemetric measurement of intragastric pH constitutes a simple method for assessing the activity of surface antacids and antisecretory agents in man. The time during which the intragastric pH is maintained at 3.5 or above is the bet criterion of therapeutic effectiveness. One hundred and fifty-two measurements were performed to evaluate the effects of six antacids administered in the usual doses and of cimetidine, milk (250 ml) and a standard continental breakfast. The results showed that the effects of antacids were extremely brief (less than 30 minutes). The delay in onset of cimetidine activity (more than 45 minutes) and the time it maintained intragastric pH above 3.5 were determined. These in vivo results correlated positively with in vitro measurements. The authors suggest that the dosage of surface antacids should be expressed in anti-acid mEq, knowing that 50 mEq produce as therapeutic effect lasting approximately 30 minutes. The data provided by radiotelemetry could be used to adjust the anti-acid treatment to the diet and the time of the day. The method also seems to be applicable to the study of new antacids and antisecretory drugs.

Double blind multicentre comparison of omeprazole 20 mg once daily versus ranitidine 150 mg twice daily in the treatment of cimetidine or ranitidine resistant duodenal ulcers.

The purpose of the present study was to compare omeprazole 20 mg once daily and ranitidine 150 mg twice daily in healing duodenal ulcers unhealed by previous treatment with cimetidine greater than or equal to 0.8 g or ranitidine greater than or equal to 0.3 g daily for at least six weeks. In a double blind multicentre trial, 151 patients were randomly assigned to either omeprazole or ranitidine. Clinical assessments and endoscopies were carried out at two and four weeks. Patients characteristics were similar in both groups. Statistical analysis (chi 2 test) did not show any significant difference in healing rate (p greater than 0.20) irrespective of the method of calculation. On an 'intent-to-treat' analysis (n = 151), healing was: omeprazole 46.6%, ranitidine 43.3% at day 15 and omeprazole 70.7%, ranitidine 68.4% at day 29; and among the patients who completed treatment, healing was: omeprazole 48.3%, ranitidine 46.3% at day 15 (n = 125; 95% confidence interval of the difference--17 to 21) and omeprazole 79.6%, ranitidine 75.4% at day 29 (n = 115; 95% confidence interval of the difference--13 to 21). After a further four weeks treatment with omeprazole, healing occurred in 16/20 (80%) who still had active disease at day 29. Patients on omeprazole and on ranitidine experienced similar decrease in day time and night time epigastric pain and in heartburn. Multivariate analysis (logistic regression) did not indicate any influence on age, sex, smoking and alcohol habits, previous drug administered, duodenitis and duodenal erosions on the healing rate. In this model, healing rate was not significantly influenced by previous treatment duration (p = 0.09 at day 15 and p greater than 0.2 at day 29) but was significantly influenced by ulcer size (p = 0.04 at day 15 and p = 0.02 at day 29). Forty one patients complained of adverse events: 19 on omeprazole (four trial withdrawals), 22 on ranitidine (three trial withdrawals).

[Serum lipoproteins in chronic alcoholics. Changes in HDL, VLDL and LDL as a function of the degree of hepatic involvement]. / Lipoprotéines sériques chez les éthyliques chroniques. Variations des HDL, VLDL et LDL en fonction du degré d'atteinte hepatique.

Changes in lipoprotein fractions HDL and LDL-VLDL were investigated in 84 chronic alcoholic patients and attempts were made to correlate these changes with the severity of liver damage. In 40 patients with undetectable hepatic lesions the lipoprotein fractions were not reduced but a rapidly reversible increase in HDL was noted in 15%. The 14 patients with steatosis and alcoholic hepatitis showed a fall in HDL, often associated with an increase in plasma triglycerides; these changes regressed during weaning. The 30 patients with cirrhosis of the liver had irreversibly low HDL and LDL levels.

Effectiveness of omeprazole in seven patients with Zollinger-Ellison syndrome resistant to histamine H2-receptor antagonists.

The inhibitory effect of omeprazole, a benzimidazole derivative, on gastric acid secretion was investigated in seven patients with Zollinger-Ellison syndrome resistant to treatment with large doses of histamine H2-receptor antagonists administered alone or in combination with pirenzepine. In two patients with an acute form of the syndrome, rapid control of acid overproduction was achieved with 180-mg intravenous and 120-mg oral daily doses, respectively. The other five patients, who were free of complication, initially received a standard regimen of omeprazole 60 mg orally once a day; dosage was subsequently adjusted until the basal acid output, measured 1 hr before the next dose of the drug, was less than 10 mmol/hr. The initial daily dose proved to be adequate in three patients and had to be increased to 80 mg and 60 mg bid, respectively in the remaining two patients. In all patients omeprazole therapy resulted in clinical recovery and rapid healing of mucosal lesions. The seven patients have now been followed up for 4-24 months (average 15 months). The adequacy of the daily dosage was periodically reassessed by measuring basal acid output in the hour preceding the morning dose. In one patient initially treated with 180 mg/day, dosage could be reduced to 60 mg/day. In three others, who were initially controlled with 60 mg/day, dosage had to be increased during follow-up. Despite adequate control of gastric acid secretion, one patient underwent total gastrectomy and tumor resection and another died of extensive liver metastases. The five patients still receiving omeprazole remain free of symptoms and mucosal lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical development of ondansetron for use in the prevention and treatment of postoperative nausea and vomiting.

An international clinical trial programme has been established to assess the efficacy and safety of ondansetron in the prevention and treatment of postoperative nausea and vomiting. The programme included nine pilot studies and six key placebo-controlled studies. These studies have evaluated both oral and intravenous formulations of ondansetron in the prevention of postoperative nausea and vomiting, and intravenously administered ondansetron in the treatment of established symptoms. Most patients included in the trials were adult women, less than 50 years of age, receiving anaesthesia for gynaecological surgery. The primary efficacy analysis for emesis was based on the assessment of complete response (i.e. absence of emetic episodes or nausea in the first 24 h postoperatively). These trials clearly demonstrated the anti-emetic efficacy of ondansetron in the prevention and treatment of postoperative nausea and vomiting.