Intragastric Acidity Research Articles

Repeated Intravenous Bolus Injections of Omeprazole: Effects on 24-Hour Intragastric pH, Serum Gastrin, and Serum Pepsinogen A and C

We determined the effect of four times daily dosing with intravenous omeprazole on 24-h intragastric acidity, serum gastrin, and serum pepsinogen A and C in 10 fasting subjects (median age, 23.5 years). Two dose regimens (80-20-20-20 mg and 80-40-40-40 mg) were compared in a randomized placebo-controlled crossover study. Intragastric pH was continuously monitored during 24 h, using combined glass electrodes, and blood samples were taken every 6 h. Repeated boluses of omeprazole every 6 h significantly increased (p less than 0.01) the median 24-h intragastric pH compared with placebo (median pH, 3.7 (140 mg/day), 4.3 (200 mg/day), and 1.4 (placebo)) but failed to continuously raise pH levels above 4.0 in 8 (140 mg/day) or 9 (200 mg/day) of 10 subjects. No advantage of the 200-mg dose over the 140-mg dose was demonstrated. A cumulative effect of intravenous omeprazole was shown after repeated boluses but also a marked interindividual variation in response, which was correlated with the omeprazole area under the plasma concentration time curve. A significant elevation of serum gastrin coincided with the increased pH levels, which was followed after 12-18 h by a significant increase of both serum pepsinogens.

24-Hour intragastric acidity and plasma gastrin after omeprazole treatment and after proximal gastric vagotomy in duodenal ulcer patients

The relationship between suppressed gastric acidity and the increase in plasma gastrin levels after pharmacological and surgical treatment of peptic ulcer disease were compared in this study. Eight patients with chronic duodenal ulcer and referred for proximal gastric vagotomy were studied. 24-hour intragastric acidity and plasma gastrin levels were investigated in the same patients on three consecutive occasions: preentry without any treatment; after 4 weeks of administration of 20 mg of omeprazole daily, and 4–6 months after proximal gastric vagotomy. Intragastric acidity was slightly more reduced by omeprazole (94%) than after proximal gastric vagotomy (78%), with no difference found during the day or night with either. Plasma gastrin levels increased slightly more after proximal gastric vagotomy [284% (median, 2120 pmol · h/L; range, 733–2831 pmol · h/L)] than after omeprazole administration [186% (median, 1586 pmol · h/L; range, 495–2573 pmol · h/L)]. There is strong evidence that the increased plasma gastrin concentration following omeprazole treatment is caused by the reduced intragastric acidity. The slight increase in plasma gastrin concentration following proximal gastric vagotomy despite a lesser reduction in intragastric acidity may be the result of additional effects on gastrin release by the vagotomy. Both treatments resulted in a modest increase in plasma levels of gastrin that were far below the gastrin levels observed in achlorhydric patients, e.g., patients with pernicious anemia.

Cigarette smoking, gastric acidity and peptic ulceration

The influence of cigarette smoking on intragastric acidity was assessed in duodenal ulcer patients in symptomatic remission and in healthy volunteers in a retrospective study. Continuous 24-hr pH recordings in 150 nonsmokers and 174 smokers receiving placebo treatment were compared. Daytime intragastric acidity was higher in smokers with a median pH (interquartile range) of 1.56 (1.34-1.80) than in nonsmokers, who had a median pH of 1.70 (1.45-1.97) (P less than 0.001). There was no difference in 24-hr and nighttime median pH between the two groups. The small difference in daytime intragastric acidity in smokers and nonsmokers is unlikely to account for the increased prevalence of peptic ulcer disease in smokers. The analysis of smoking status in duodenal ulcer patients and healthy controls and males and females supports the general trend towards higher daytime acidity in smokers. Again, no differences in pH during the 24-hr or night period were found between the groups. The epidemiological and clinical correlation between smoking and duodenal ulcer disease is not adequately explained by increased intragastric acidity.

EFFECT OF ORAL OMEPRAZOLE ON INTRAGASTRIC pH AND VOLUME IN WOMEN UNDERGOING ELECTIVE CAESAREAN SECTION

We have studied in obstetric patients the efficacy of omeprazole in increasing intragastric pH to more than 2.5 and reducing volume to less than 25 ml. Omeprazole 40 mg was given orally the night before and again on the morning of surgery to 30 Asian women scheduled to undergo elective Caesarean section. After induction of anaesthesia, a gastric tube was inserted and intragastric contents aspirated. Volume and pH were recorded and measurements were repeated on completion of surgery. The median (range) volume was 2 (1-13) ml before surgery and 4 (0-14) ml at the end of surgery. There was insufficient volume to measure pH in all patients. The median (range) pH was 6.7 (4.6-7.4) before surgery in 20 patients and 6.6 (4.6-7.8) at the end of surgery in 28 patients. No adverse drug reactions were noted in mothers or neonates. Omeprazole 40 mg orally twice before elective Caesarean section appeared to be effective in reducing intragastric volume and acidity to acceptable values.

The timing of the evening meal affects the pattern of 24‐hour intragastric acidity

The object of the study was to examine the effect of varying the time of the evening meal on the pattern of 24-h intragastric acidity. Ten healthy subjects were studied; they ate regular meals throughout the day, but between 17.00 and 21.35 hours were separated into three groups. On three different days each group was fed the same dinner at either 17.15, 19.15, or 21.15 hours (early, standard or late). Variation in the evening meal's time caused significant changes in the pattern of acidity in the afternoon and evening, but did not affect 24-h intragastric acidity or nocturnal acidity. Integrated afternoon acidity (14.00 hours to dinner) was 69, 169 and 324 mmol.h/L when the subjects ate early, standard and late meals, respectively; evening acidity (dinner to midnight) was 235, 43 and 1 mmol.h/L with the three meals, respectively. The results suggest that, to control intragastric acidity, when the evening meal is eaten early (17.15 hours) dosing with an H2-antagonist should be after that meal, when eaten at the standard time (19.15 hours) dosing should be at bedtime, but when dinner is late (21.15 hours) the optimal regimen may involve dosing after lunch and also at bedtime.

Prolonged inhibition of acid secretion causes hypergastrinaemia without altering pH inhibition of gastrin release in humans

Hypergastrinaemia induced by potent inhibitors of acid secretion is thought to occur as a result of the elimination of the inhibitory effects of intragastric acid on gastrin release. The present study was designed to determine if the mechanisms responsible for feedback inhibition of gastrin release and acid secretion by intragastric acid are preserved during four weeks of varying degrees of drug-induced acid inhibition. Forty-eight healthy male volunteers were randomly assigned to one of four treatments for four weeks: 10 mg omeprazole o.m., 20 mg omeprazole o.m., 40 mg omeprazole o.m. or 150 mg ranitidine b.d. Gastrin release and acid secretion in response to peptone meals maintained at pH 2.5 and pH 5.5 by intragastric titration, and 24-hour gastrin profiles in response to standard meals were determined before treatment, at the fourth week of treatment and two weeks after discontinuing treatment. As expected, omeprazole produced dose-related effects on acid secretion and gastrin concentrations that were largely reversed after treatment was discontinued. Gastrin release in response to pH 5.5 peptone meals remained significantly greater than gastrin release in response to pH 2.5 meals during treatment with all doses of omeprazole. The ratio of pH 5.5/pH 2.5 peptone meal-stimulated gastrin release was approximately 1.5, and remained constant for all treatment groups throughout the study period. These data indicate that four weeks of drug induced hypochlorhydria causes an apparent increase in overall G-cell function, but it does not interfere with normal feedback inhibition of gastrin release and acid secretion mediated by intragastric acidity.

Twenty‐four‐hour intragastric acidity and nocturnal gastric secretion in gastric ulcer patients—the effects of cimetidine

In a double-blind randomized study, the profile of 24-h intragastric acidity and nocturnal gastric secretion was measured in a group of patients with healed gastric ulcer on placebo and 400 mg cimetidine b.d. and 800 mg nocte. Neither cimetidine regimen significantly decreased daytime intragastric acidity, but the 800 mg nocte dose caused a significant decrease in both nocturnal acidity (18.1 to 5.5 mmol/L; P less than 0.05) and acid output (11.0 to 1.7 mmol 7 h; P less than 0.05). The decrease in nocturnal gastric secretion by 400 mg cimetidine b.d. was not significant. As in duodenal ulcer, 800 mg cimetidine nocte will effectively suppress night-time acid secretion in patients with gastric ulcer while leaving acid secretion during the day unaffected.

Inappropriate hypergastrinaemia in asymptomatic healthy subjects infected with Helicobacter pylori.

An ELISA test determined serologically that eight of 95 apparently healthy men (aged 19-26 years) had an asymptomatic infection with Helicobacter pylori at the time of simultaneous measurement of 24 hour intragastric acidity and 24 hour plasma gastrin concentration. There was no significant difference in the median integrated 24 hour intragastric acidity between the H. pylori positive and H. pylori negative subjects (688 and 842 mmol/h/l; p = 0.271, respectively), whereas the median integrated 24 hour plasma gastrin concentration was significantly higher in the H pylori positive than in the H pylori negative subjects (389 and 198 pmol/h/l; p less than 0.001). Longterm hypergastrinaemia, associated with persistent H pylori infection, could be a cause of the increased parietal cell mass that is considered characteristic of duodenal ulcer patients.

Pharmacokinetics and bioavailability of omeprazole after single and repeated oral administration in healthy subjects.

1. Ten healthy subjects were given 20 mg omeprazole EC (enteric coated) granules once daily for 8 days. An i.v. tracer dose of [14C]-omeprazole was given simultaneously with the first and last oral doses and blood sampling was performed thereafter. In order to study the extent of absorption at minimal acid exposure, a single dose of 20 mg omeprazole was also given as a buffered solution, before and after the treatment with EC granules. 2. Kinetic parameters of omeprazole after the i.v. tracer dose were unchanged on repeated dosing while AUC increased by approximately 40% for the solution and 60% for the EC granules. 3. The increased AUC is caused by an increased systemic availability, which may be explained by a decreased first-pass elimination during repeated treatment and/or by a reduced degradation of omeprazole in the stomach secondary to the profound decrease in intragastric acidity caused by the drug. 4. The implication of these findings is that the antisecretory effect of therapeutic doses of omeprazole must be studied during repeated administration and not judged from studies using single doses only.

Clofibrate raises human 24 h intragastric acidity but does not affect plasma gastrin concentration.

1. We studied the effects of acute oral dosing with clofibrate (500 mg four times daily) on 24 h intragastric acidity and plasma gastrin concentration in 12 healthy female subjects. 2. The 24 h integrated intragastric acidity rose from 429 mmol l-1 h (95% CI 296-479) before dosing to 527 mmol l-1 h (95% CI 385-664) on the day of dosing (+23%; P = 0.041), but no change was observed in the 24 h integrated plasma gastrin concentration: 420 pmol l-1 h (95% CI 282-499) before and 389 pmol l-1 h (95% CI 249-489) during dosing (P = 0.182). 3. We conclude that clofibrate has no acute antisecretory effect on the human stomach, and that human gastrin-induced enterochromaffin-like cell proliferation is unlikely with this drug.

Effect of Single-Dose Omeprazole on Intragastric Acidity and Volume During Obstetric Anaesthesia

Department of Anaesthetics, Belfast Hospital, Queen's University of Belfast and Ulster Hospital, Belfast, Northern Ireland; and Astra Clinical Research Unit, Edinburgh, Scotland

Sufotidine 600 mg bd virtually eliminates 24 hour intragastric acidity in duodenal ulcer subjects.

In a double blind study, 24 hour intragastric acidity and 24 hour plasma gastrin concentrations were measured simultaneously in seven duodenal ulcer subjects on the fifth day of receiving either sufotidine 600 mg bd or placebo. Compared with placebo, during treatment with sufotidine 600 mg bd the median integrated 24 hour intragastric acidity was decreased by 95% (range 74% to 99%) from 1000 to 51 mmol/h/l, whilst the median integrated 24 hour plasma gastrin concentration increased from 416 to 927 pmol/h/l.

Drug-Induced Changes of Plasma Gastrin Concentration

There is a significant inverse relationship between intragastric acidity and plasma gastrin concentration. All generally available gastric acid antisecretory drugs induce a release of gastrin into the circulation. The more potent the gastric antisecretory dosage regimen or drug, the greater the rise of plasma gastrin concentration. The drug-induced rise of plasma gastrin concentration is of no direct clinical concern, although it may be partly responsible for the phenomenon of tolerance to H2-blockade. Drug-induced hypergastrinemia could stimulate the proliferation of certain cell lines associated with the gastrointestinal tract, for example, the gastric epithelium, ECL cells, or colonic neoplasms.

Intravenous omeprazole: effect of a loading dose on 24‐h intragastric pH

To determine the effect of three times daily dosing with intravenous omeprazole on intragastric acidity, 24 h intragastric pH was measured continuously with a monocrystalline antimony electrode system in II patients with inactive duodenal ulceration during fasting conditions. After a baseline investigation, two different dosage regimens of intravenous omeprazole were compared in a double-blind crossover study, with regard to their ability to keep the pH greater than or equal to 4 for as long as possible. Success in the individual patient was defined as pH greater than or equal to 4 for at least 90% over the 24-h period. Two doses of omeprazole [40 mg t.d.s. (120 mg) and 80 mg + 40 mg + 40 mg (160 mg)] were compared. Omeprazole (120 mg) increased the median of individual median intragastric 24-h pH from 1.49 to 6.67. The pH was greater than or equal to 4 for greater than or equal to 90% of the 24 h in three of the 11 patients. With omeprazole, 160 mg (a loading dose of 80 mg), the median of individual median intragastric 24-h pH increased to 7.33. The pH was greater than or equal to 4 for greater than or equal to 90% of the 24 h in seven of the 11 patients. Median time to reach pH 4 was 39 min after 40 mg and 20 min after 80 mg omeprazole. An initial loading dose of 80 mg omeprazole seems preferable to 40 mg to achieve a fast and sustained increase in intragastric pH to above 4 in the fasting patient.

Effect of food on H2-receptor blockade in normal subjects and duodenal ulcer patients.

Two separate studies of 24 hour intragastric acidity were carried out in normal volunteers and duodenal ulcer patients to define the interaction of food and the antisecretory effects of H2-receptor blockers. Both investigations were double blind randomised comparisons using ranitidine 300 mg with either different meal times or ad libitum snacks after an evening meal. Meals taken after drug administration nearly abolished measurable antisectory effects. Median 24 hour pH was 1.3 on placebo, 2.6 when ranitidine was administered after the evening meal and 1.9 when administered before the evening meal. Snacks taken after evening dosing with ranitidine also significantly decreased pharmacodynamic efficacy. During placebo, median night-time pH was 1.3 without snacks and 1.4 with snacks. pH rose to 5.9 during ranitidine treatment when snacks were forbidden but was only 3.1 when snacks were allowed. These findings could be of therapeutic importance and should rationalise dietary advise to patients receiving H2 blockers. The timing of drug administration can be adjusted according to individual life styles.

The relationship between suppression of acidity and gastric ulcer healing rates

We have investigated the relationship between the suppression of acidity by antisecretory drugs for the treatment of benign gastric ulcer and their corresponding ulcer-healing rates. For a variety of antisecretory drug regimens, there was a significant correlation between suppression of 24-h intragastric acidity and ulcer healing rates after 2, 4 and 8 weeks of treatment. There was a lesser degree of correlation between healing and suppression of nocturnal acidity and the association between suppression of acidity and gastric-ulcer healing rates was less marked than that previously described for duodenal ulcer.

Acute Erosions of the Gastric Mucosa in Burned Rats: Effect of Gastric Acidity and Fluid Replacement

Early changes in the morphology of the gastric mucosa after the skin had been burned were studied using a standardised model in rats. A full thickness burn was inflicted by exposing about 20% of the total body surface area to hot water (99 degrees C) for 10 s. Intragastric acidity was kept at pH 1.0 or pH 7.4 in six experimental groups of eight rats. Rats were subjected to burns with the stomach irrigated at pH 1.0 or pH 7.4. Parallel groups received fluid replacement with a solution of human albumin, and two uninjured groups served as controls. Lesions of the gastric mucosa were measured by planimetry of photographs, and light microscopy was used for histological examination. At an intragastric pH of 1.0, the burned rats developed mucosal erosions covering an average of 13% of the total glandular mucosa; the remaining groups had only minimal mucosal lesions. Erosions of the gastric mucosa after the skin had been burned could be prevented in two ways--either by establishing an alkaline (pH 7.4) milieu in the gastric lumen, or by replacing sufficient fluid to maintain aortic blood pressure at the pre-experiment level. Fluid replacement prevented mucosal erosions even if the intragastric pH was kept at 1.0. Thus both luminal acidity and local tissue blood flow are possible mechanisms for gastric epithelial damage following burns of the skin.

24H Intragastric Acidity and Plasma Gastrin Concentration in Female and Male Subjects

24H Intragastric Acidity and Plasma Gastrin Concentration in Female and Male Subjects

Fasting Levels of Serum Gastrin in Different Functional and Morphologic States of the Antrofundal Mucosa: An Analysis of 860 Subjects

The relationship of fasting serum gastrin (FSG) levels to the histologic state of antral and body mucosa and to the stimulated acid output (PAO) was examined in 860 subjects. The FSG levels correlated with PAO and atrophy of the body mucosa: the FSG increased linearly with an increase in the grade of body atrophy and increased exponentially when the PAO decreased from 'normal' (greater than 10 meq/h) to zero. In subjects with achlorhydria or marked hypochlorhydria (PAO less than 1.1 meq/h) accompanying moderate or severe atrophy in the gastric body mucosa, FSG decreased linearly with increasing grade of atrophy in the antral mucosa. No such relationship between antral atrophy and FSG was found in subjects who had a PAO above 1.1 meq/h or who had non-atrophic gastric body mucosa. We conclude that the state of the antral mucosa influences the FSG level, but only when the function of antral G cells is maximal--that is, in achlorhydric or nearly achlorhydric conditions in which the inhibitory effect of intragastric acidity on the G cells' secretion of gastrin into the circulation is minimal.

Gastric Aspiration Technique for pH Recording: A Critical Evaluation of This Method

The most often used methods for the measurement of intragastric acidity are repeated mostly hourly aspirations of gastric contents or continuous pH measuring with an electrode. Intragastric pH, volume of aspirated gastric juice and total acid secretion have been tested over relatively short periods of time (2-12 h) and through an entire 24-hour period. Nearly every clinical antiulcer drug which neutralizes acidity or inhibits acid secretion has been investigated with this method. pH monitoring with the gastric aspiration procedure is a reliable and reproducible method. There is a remarkable global agreement in the results. While pH electrodes provide an alternative means of measuring pH, they have the disadvantage of not allowing measurement of volume and/or acid secretion.