[Treatment of gastric acid hypersecretion in the Zollinger-Ellison syndrome with a thioamide derivative (40749 RP). Comparison with ranitidine]. / Traitement de l'hypersécrétion gastrique acide du syndrome de Zollinger-Ellison par un dérivé des thioamides (40749 RP). Comparaison avec la ranitidine.

The efficacy of a new gastric antisecretory drug, 40749 RP, was studied in five cases of Zollinger-Ellison syndrome. Daily oral dosage was 2 mg/kg bw b.d. Clinical results and tolerance were excellent in all five cases (follow-up 1 to 16 months). In two cases, chronic duodenitis disappeared with 40749 RP only. Antisecretory activity was evaluated on basal acid output and 24 h pH profile. During 24 h period, the mean number of hours at or below pH 1.5, 2 and 3 obtained with 40749 RP in the five cases was 5, 9 and 12 h versus 13, 14 and 19 h with ranitidine. In all cases, basal acid output measured during one hour before fractional intake of 40749 RP was below 7 mmol/h during the first month of treatment. Clinical and biological results obtained with 40749 RP are similar to those obtained with omeprazole.

[How to express results of 24-hour gastric pH measurement? Choice of a mode of expression in 27 healthy subjects]. / Comment exprimer les résultats de la pH-métrie gastrique sur 24 heures? Choix d'un mode d'expression chez 27 sujets sains.

Twenty-four hour intragastric acidity was studied in 27 healthy subjects (mean age = 29 yrs) by continuous recording in standardized conditions. Data obtained were expressed according to several analytical methods as used extensively elsewhere. In our study, there was a wide discrepancy in results from one subject to another. The use of median values of pH was more appropriate than mean values to express half-hour acidity levels for 24 hours. The median value of H+ concentration is recommended as well. The median value of pH varied from 1 to 4.8 with a slight rise during the second half of the night. During the postprandial period, increase of pH values was prolonged over 2 h 30 in 50 p. 100 of subjects. Profile of pH allowed to demonstrate the distribution of pH value without excluding the extreme values. Both periodicity of pH measurement (30 or 60 min) and parameters used to quantify acidity (percentage of time or pH value at or below threshold values) did not modify results. As measured over a 24 hours period, the percentage of time (mean +/- SEM) at or below pH 1.5 and 3.5 was 54 +/- 3 p. 100 and 85 +/- 2 p. 100, respectively. Daytime and night-time profiles were similar. Mean 24 h H+ concentration (mean +/- SEM) was 47 +/- 35 mmol/l, with, once again, similarity between day and night-time values. The mean 24 h pH values underestimated true acidity with respect to median values.(ABSTRACT TRUNCATED AT 250 WORDS)

[Efficacy of a new antisecretory agent (40 749 RP) on human gastric secretion induced by a meal (intragastric titration)]. / Efficacité d'un nouvel antisécrétoire (40 749 RP) sur la sécrétion gastrique de l'homme induite par le repas (titration intra-gastrique).

An antisecretory drug of a new series, 40 749 RP, without anticholinergic or H2 receptor antagonist activities, was tested on meal-induced gastric acid secretion in 6 healthy volunteers. Gastric acid secretion and emptying of liquid were measured using intragastric titration. Oral dosages tested were 1, 2 and 4 mg/kg versus placebo. Inhibitions obtained were dose-related and expressed in percentage of the placebo values: 36 +/- 10 p. 100 for 1 mg/kg; 51 +/- 13 p. 100 for 2 mg/kg and 83 +/- 5 p. 100 for 4 mg/kg. Statistically significant correlation (p less than 0.001) was observed between maximal blood concentration of 40 749 RP and the percentage of secretory inhibition during the 90 min of the test. No change in gastrin response or in gastric emptying was observed whatever the dose.

Acute and chronic 24-hour gastric pH and pharmacokinetic studies with a long acting antisecretory drug (40749 RP) in peptic ulcer.

The purpose of this work was to compare the effects of a long acting antisecretory drug on 24-h gastric acidity after acute and chronic administration and to correlate the results observed with modifications of pharmacokinetic parameters. 40749 RP is a carbothioamide derivative antisecretory drug with a non anti H2, non anticholinergic mechanism of action. Eleven patients with an endoscopically proven duodenal ulcer received 100 mg of 40749 RP at 8 PM for 3 wk and thereafter a placebo for an additional 3 wk study period. At the end of the active drug treatment period all patients but one had healed. Continuous 24-h gastric pH recordings performed after the first and the last dose of 40749 RP showed a strong and yet still increasing acid inhibition, nine patients being nearly achlorhydric (i. e. pH greater than 3) during night at the end of treatment. Variations of acid inhibition between the start and the end of treatment were significantly correlated with modifications of pharmacokinetic parameters. Eight days after discontinuation of 40749 RP, basal acid secretion remained strongly inhibited. However at the end of the placebo period, endoscopy showed ulcer relapse in 4 patients (previously resistant to H2-blockers). These results confirmed that 40749 RP is a powerful and very long-acting antisecretory drug. They showed that the antisecretory effects of a long-acting drug should be assessed in conditions of chronic administration when therapeutic dose and regimen are to be determined.

[Influence of ranitidine during a 24-hour period on the level of nitrites, nitrates, nitrosamines and bacterial flora in the gastric juice of healthy subjects]. / Influence de la ranitidine durant une période de 24 heures sur la teneur en nitrites, nitrates, nitrosamines et sur la flore bactérienne du suc gastrique du suject sain.

The aim of this study was to determine the influence of 24 h of ranitidine treatment on gastric bacterial flora and N-nitroso compound formation. Nitrate, nitrite levels, N-nitroso compound concentration were measured and bacterial flora was studied in the fasting and postprandial gastric juice of four healthy men under placebo and ranitidine treatment (150 mg. bid). The pH of seventy-five per cent of the gastric juice samples was over 4 when the patients received their ranitidine treatment. While the mean intragastric concentrations of nitrate, nitrite, N-nitroso compounds and counts of nitrate-reducing organisms were not significantly altered by ranitidine, there was a statistically significant rise in the number of total bacteria. During ranitidine treatment, the nitrite/nitrate ratio was positively correlated with intragastric pH and with the nitrate-reducing organism count of the placebo period. These results suggest that the reduction of nitrate to nitrite required the combination of two factors: a high count of nitrate-reducing organisms before treatment and a high intragastric pH.

[The effect of ranitidine on gastric pH measured by continuous monitoring over 24 hours in healthy subjects. Comparison of 2 methods of administration: 150 mg morning and night, vs 300 mg in a single dose at night]. / Effet de la ranitidine sur le pH gastrique mesuré par enregistrement continu sur 24 heures chez le sujet sain. Comparaison de deux modes de fractionnement: 150 mg matin et soir, vs 300 mg en prise unique le soir.

The gastric pH of 8 healthy subjects was determined, in a continuous fashion, during three different 24 hour periods corresponding to the 3 following treatments: Placebo, ranitidine 150 mg twice per day, and ranitidine 300 mg in the evening. During each period, the feeding conditions were normal and standardized. The results are expressed in terms of the number of hours under a threshold pH value. In comparison with the placebo, ranitidine, regardless of its mode of administration, results in a significant decrease of the mean number of hours under pH 1.5, 2 and 3 during 24 hours; no significant difference was demonstrated between the two modes of administration in 24 hours. During the 12 night-hours, a single dose of 300 mg of ranitidine was more effective to ranitidine taken in 2 doses for pH thresholds of 2 and 3, while during the 12 day-hours, no difference was demonstrated for pH thresholds of 1.5, 2 and 3. The analysis of the mean pH graphs in relation to time, suggests that a single 300 mg dose is more effective than the same dose divided into 2 doses during the day. These results tally with the variations of ranitidine plasma levels in 24 hours. These results justify, from a pharmacological standpoint, the prescription of a single dose of ranitidine, in the evening.

Helicobacter pylori en sujetos asintomáticos, con úlcera duodenal, úlcera gástrica y dispepsia no ulcerosa en Cartagena

OBJETIVOS. Determinar la prevalencia de la infección de Helicobacter Pylori (HP) en sujetos asintomáticos (A) y pacientes con úúlcera duodenal (UD), úlcera gástrica y dispepsia no ulcerosa (DNU) en la Ciudad de Cartagena. METODOS: Se estudiaron 90 pacientes a los que se les practicó endoscopia digestiva con toma de biopsia para cultivo y coloraciones especiales. RESULTADOS: Se logró demostrar el HP en sujetos asintomáticos (50 por ciento); UD:96 por ciento, UG:90 por ciento; DNU:85.7 por ciento. CONCLUSION: Se demostró la alta prevalencia del HP en distintos grupos en la Ciudad de Cartagena. Este es el primer estudio realizado en la Costa Atlántica de nuestro país