Drug interactions with diosmectite: a study using the artificial stomach-duodenum model.

Drug interactions with diosmectite, a gastric-protective drug, were studied in vitro using an artificial stomach-duodenum model. The behavior of neutral and ionisable drugs with pKa values ranging between 2 and 8 was monitored to determine the physicochemical characteristics of the interactions. The main neutral (digoxin) and acid (valproic acid) drug substances were moderately fixed by clay (<27%), in a pH-independent manner.

Interests of the 'artificial stomach' techniques to study antacid formulations: comparison with in vivo evaluation.

In this overview, the methods for assessing antacid activity in vitro are surveyed, and the problems of their comparison with in vivo methods of evaluation are discussed. In vitro assessment is based on two types of method: static and dynamic. The static method of titration, with end-of-titration pH values ranging between 3.

In vitro assessment of antacid efficacy using a computer-controlled 'artificial stomach-duodenum' model reproducing gastroduodenal flux regulation.

We have developed an artificial stomach-duodenum model made up of three compartments representing the stomach, (including a fragment of hog gastric mucosa), the proximal duodenum, and the distal duodenum. Gastroduodenal flow rates are controlled by a microcomputer capable of (1) adjusting gastric emptying and alkaline secretion in the proximal duodenum according to intragastric pH; (2) adjusting pancreatic alkaline secretion according to proximal duodenum pH; and (3) simulating acid response to food ingestion. Antacid drugs were added 90 min after simulated food ingestion in near-physiological or duodenal ulcer conditions.

[Antacid activity of citrate-bicarbonate complex of effervescent formulations of ranitidine. In vitro analysis using 'artificial stomach-duodenum' model].

Antacid activity supported by citrate-bicarbonate complex of four effervescent ranitidine forms has been assessed in vitro using an 'artificial stomach-duodenum' model controlled by microcomputer. This model allows (i) maintenance of constant the rates of the fluxes throughout the experiments or (ii) simulation of gastroduodenal flux regulation, in the normal subject (NS) or in the duodenal ulcer patient (DU) situation. The four forms developed a theoretical maximal antacid capacity between 61 and 81 mmol with a maximum intragastric pH between 3.

Effect on gastric secretion, gastrin and histamine release during and after long-term treatment by pirenzepine in dogs.

We assessed the effects of pirenzepine (2 mg/kg per os) on gastric secretion and gastrin and histamine release in response to food and histamine dihydrochloride infusion in four dogs during 24 weeks of treatment and for 15 weeks after the end of treatment. The results were compared to those obtained in the same animals in control experiments, before treatment, and in four untreated dogs. Pirenzepine absorption was checked by measuring plasma concentrations.

[Factors of gastroesophageal acid reflux in severe obesity].

Objective: To study in morbid obesity the relationship between the degree of gastro-oesophageal reflux (GER) and the excess of body weight, or the related factors such as the energy intake or the fat distribution (waist-hip ratio).

Methods: In 20 morbid obese subjects (body weight: 125 +/- 32 kg) consulting in a weight-loss programme, anthropometric measurements, 3-hr oesophageal pHmetry, double isotope labelled meal for studying gastric emptying, study of gastric acid and pepsin secretions using PEG 4,000 as marker, and upper endoscopy were performed.

Results: Nine out of the 20 patients had more than 10 GER per 3-hr period.

Characteristics and consequences of duodenogastric reflux in children on total parenteral nutrition (TPN) for severe gastrointestinal disorders.

This study was carried out to determine the frequency and composition (biliary and/or pancreactic) of duodenogastric reflux (DGR) in children with severe gastro-intestinal disorders on total parenteral nutrition (TPN), and to assess its consequences in terms of gastric histology (gastric per endoscopic biopsies) and secretion (acid, pepsin and sialic acid output). Sixteen children (mean age: 20 months) with severe gastro-intestinal disorders requiring TPN (mean duration: 9.5 months) were studied.

Interactions of cimetidine and ranitidine with aluminum-containing antacids and a clay-containing gastric-protective drug in an "artificial stomach-duodenum" model.

Interactions of cimetidine and ranitidine with aluminum-containing antacids and clay-containing gastric-protective drugs were analyzed in vitro by using an artificial stomach-duodenum model. The model reproduced near-physiologic conditions, taking into account gastric and duodenal flux variations and interactions between gastric mucosa and drugs added to the gastric content. Clay bound cimetidine in acid medium, but the drug was released when the pH increased, resulting in cimetidine amounts in the duodenal site close to those in controls.

Antacid activity of calcium carbonate and hydrotalcite tablets. Comparison between in vitro evaluation using the "artificial stomach-duodenum" model and in vivo pH-metry in healthy volunteers.

Antacid activity of calcium carbonate (CAM, Rennie) and of hydrotalcite (HYD) containing tablets has been assessed in vitro using computer-controlled "artificial stomach-duodenum" model, including or not a piece of hog gastric mucosa in the gastric reservoir, and simulating the constant flux system or the normal gastroduodenal flux regulation. The data obtained under the latter condition were compared to those obtained in vivo by pH-metry in 12 healthy volunteers, in response to one administration of 2 tablets. The theoretical maximal capacity was similar when 1 tablet of CAM or of HYD was added to the gastric contents, including or not a piece of gastric mucosa, close to 95 H+ mmol.

[Cephalic phase of gastric secretion in dogs. Effect of palatability and caloric intake].

The purpose of this study was to analyze the relative part of the cephalic phase in the gastric secretory and circulating gastrin responses to meals of variable composition and palatability in dogs. Meal palatability was quantified by measuring the ingestion rate of a fixed amount of food. By progressively increasing the amount of carbohydrates or lipids added to a normal meat meal, it was possible to obtain eleven meals of progressively decreasing ingestion rate.

[Dose-response effect of lansoprazole in patients with Zollinger-Ellison syndrome].

Lansoprazole, a new substituted benzimidazole, is an effective acid proton pump inhibitor acting by inhibiting selectively H+/K+ ATPase of the gastric parietal cell. This study was performed to assess the effect of successive 30, 60, 90 and 120 mg dosages of lansoprazole in 4 patients suffering from Zollinger-Ellison syndrome. The basal gastric acid output was markedly inhibited in comparison with baseline values (mean maximal reduction: 87%; extremes: 75-99%) and was dose-related.

[The observance of Ramadan and its repercussion on gastric secretion].

The influence of the Ramadan on the gastric secretion has been assessed in 13 volunteers. Their basal and pentagastrin-stimulated secretion has been collected before, during and one month after the Ramadan. Gastric activity, pepsin activity, sialic acid bound to glycoprotein, choline and gastrinaemia have been measured.

Gastric secretion of platelet activating factor and precursors in healthy humans: effect of pentagastrin.

The release of platelet activating factor (PAF-ACETHER or PAF) and its precursors in the gastric lumen was assessed in 13 normal subjects in basal condition and after stimulation by gastrin. Acid, pepsin, and sialic acid outputs were determined under the same conditions. Gastric juice was collected using a nasogastric tube after overnight fast in basal condition for 60 minutes, then under pentagastrin infusion (6 micrograms/kg/hr for 60 minutes).

Molecular fractionation of gastric mucus component by high-performance liquid chromatography: application to pig gastric mucus in vitro and to human gastric mucus collected by aspiration during gastric endoscopy.

The glycoprotein molecular composition of antral and fundic adherent mucus has been studied by high-performance liquid chromatography on a silica gel column. Preliminary assays with pig gastric mucus allowed us to demonstrate the reproducibility of the method. The mucolytic activity of pepsin on this mucus demonstrates its ability to detect degradation of its glycoprotein components.

Treatment of patients with Zollinger-Ellison syndrome.

In the treatment of Zollinger-Ellison syndrome patients with severe disease and acid hypersecretion, proton pump inhibitors are the drugs of choice. Data have now been accumulated on lansoprazole treatment of 41 patients (21 treated at the National Institutes of Health [NIH], Bethesda, Maryland, USA, and 20 treated at the Bichat-Claude Bernard Hospital, Paris, France). Short-term studies of the inhibitory action of lansoprazole on acid secretion have been carried out in both institutions.

Evidence for the interaction between antacid and gastric mucosa using an "artificial stomach" model including gastric mucosa.

In light of evidence that certain aluminum-based antacids adhere to the gastric mucosa, we modified our previously described "artificial stomach" (AS) model by including a piece of hog stomach and compared the antacid activity of six aluminum-containing antacid products in the model with and without gastric mucosa. The activity of three of these, Maalox, Riopan and Supralox, was not significantly different in the two systems. In contrast, the activity of the other three, Aludrox, Phosphalugel and Simeco, was significantly greater with mucosa.

Significance and regulation of gastric secretion of platelet-activating factor (PAF-acether) in man.

Platelet-activating factor (PAF) has been implicated in the pathogenesis of acute inflammatory and ulcerative diseases of the upper gastrointestinal tract. In the present study, we compared the gastric output of PAF and its precursors with gastric acid output, in patients with various upper gastrointestinal tract diseases and healthy controls. PAF and precursors were also extracted from gastric biopsies from subjects with chronic gastritis and/or gastric colonization by Helicobacter pylori.

An artificial stomach-duodenum model for the in-vitro evaluation of antacids.

To improve the dynamic in-vitro evaluation of the effects of antacids, we have developed the 'artificial stomach' model by adding a 'duodenal reservoir' to receive the gastric emptying flux and simulated bicarbonate secretion, thus constituting an 'artificial stomach-duodenum' model. With this model we measured antacid-induced resistance to gastric acidification, and simultaneously evaluated the effect of antacid activity on the duodenal milieu. The model also permitted evaluation of the antacid effects of proteins (as natural antacids), and of drugs containing aluminium phosphate, alone or combined with magnesium oxide, or aluminium and magnesium hydroxides.

[In vitro evaluation of antacid activity in gastric acid secretion in static and dynamic systems].

A valid in vitro evaluation of antacid capacity should consider: 1) the intragastric pH-range; 2) the antacid mechanism; 3) the dependence of antacid activity from intraluminal flux variations; 4) the interaction between proteins and antacids. Pharmacologically, a static method allows 1) to quantify H+ binding sites at different pH-end points of the titration: pH 3.0, 2.

[Gastric secretion of pepsin in gastroesophageal reflux complicated or not with peptic esophagitis].

Few data have concerned gastric peptic activity in reflux esophagitis. Gastric basal and pentagastrin-stimulated acid, pepsin, sialic acid (marker of gastric mucus erosion) and choline (marker of duodenal refluxate) outputs were measured in 75 patients with gastroesophageal reflux. Fifty-one patients had erosive esophagitis (grade greater than or equal to II) and 24 had no esophagitis or esophagitis grade I.

Gastric secretory investigation of recurrent ulcer after surgery for duodenal ulcer.

The results of gastric secretory studies in 192 cases of recurrent ulcer after surgery for duodenal ulcer were analyzed and compared with the secretory data collected in a control group of 74 duodenal ulcer patients who had undergone various forms of gastric surgery, but who did not develop a recurrent ulcer (controls). The patients studied comprised 46 cases of recurrent ulcer after partial gastrectomy, 10 cases of recurrent ulcer after partial gastrectomy and bilateral truncal vagotomy, 56 cases of recurrent ulcer after truncal vagotomy and drainage, 52 cases of recurrent ulcer after highly selective vagotomy, and finally 28 cases in which the recurrent ulcer led to the diagnosis of the Zollinger-Ellison syndrome. The entire study was based upon an analysis of the basal acid output, the response to maximal stimulation by pentagastrin or by histalog and by insulin in the case of previous vagotomy, and finally on an assessment of basal serum gastrin.

Antisecretory and anti-ulcer effects of morphine in rats after gastric mucosal aggression.

The effects of morphine on gastric secretion, barrier mucus and mucosal lesions were studied in pylorus-ligated rats treated with the ulcerogenic agents, indomethacin, aspirin or taurocholic acid. All three ulcerogenic agents induced significant mucosal lesions. Morphine decreased gastric acid secretion and suppressed the aspirin- and taurocholic acid-induced, but not the indomethacin-induced mucosal lesions.