Twenty-four-hour intragastric acidity following early evening or bedtime administration of roxatidine in duodenal ulcer patients

Aim : To assess the usefulness of early evening administration of roxatidine 150 mg as an alternative to the traditional bedtime regimen.
Methods : Twenty-four patients with healed duodenal ulcer were dosed according to a balanced incomplete-block design, with two of the following regimens: placebo, roxatidine 150 mg at 07.30 h (early evening) or roxatidine 150 mg at 22.00 h (bedtime). Twenty-four-hour intragastric pH-metry was started at 18.00 h on the first day of dosing. Median pH was determined for the 24-h period, and for the following time intervals: 20.00–00.00 h, 00.00–08.00 h and 08.00–18.00 h. Percentage time in the 24-h period with pH greater than 4.0 was also calculated.
Results : The two roxatidine regimens proved significantly superior to the placebo, decreasing 24-h acidity for all the time intervals, except the 20.00–00.00 h period, when mean intragastric pH with the early evening regimen (4.5±1.1) proved significantly higher than after placebo (2.2±1.0) or when roxatidine was taken at bedtime (2.4±1.1).
Conclusion : Early evening administration of roxatidine may afford satisfactory control of 24-h acidity, offering a useful alternative to conventional bedtime administration.     

Twenty-four-hour intragastric acidity in duodenal ulcer patients during dosing with placebo, and 150 mg ranitidine twice or four times daily

Twenty-four-hour intragastric acidity was measured in 10 patients with a past history of duodenal ulcer on the fourth day of dosing with placebo, and either 150 mg ranitidine given twice or four times daily. The order of the treatments was randomized and a double-blind design was employed. Ranitidine (150 mg) b.d. decreased median integrated 24-h intragastric acidity by 65.1%, nocturnal acidity by 89.1%, and daytime acidity by 54.6% (all P less than 0.01 compared to placebo). The corresponding decreases with 150 mg ranitidine q.d.s. were 62.3, 89.9 and 48.8%, respectively (all P less than 0.01) compared to placebo). There were no significant differences between the two dosage regimens of ranitidine (P greater than 0.05). This study shows that giving extra doses of 150 mg ranitidine during the day does not increase the degree of suppression of intragastric acidity.     

Comparison of ranitidine 300 mg twice daily, 300 mg at night and placebo on 24-hour intragastric acidity of duodenal ulcer patients

Continuous measurement of 24-hour intragastric acidity was performed in 12 duodenal ulcer patients in remission during treatment with placebo, ranitidine 300 mg nocte and ranitidine 300 mg b.d. Median 24-hour acidity was 79.4 mmol litre-1 during placebo treatment; it decreased to 28.2 mmol litre-1 during treatment with ranitidine 300 mg nocte and to 3.6 mmol litre-1 during treatment with ranitidine 300 mg b.d. The two regimens decreased intragastric acidity to a similar degree during the night, but significantly greater inhibition of daytime and 24-hour acidity followed use of ranitidine 300 mg b.d.     

Twenty-four-hour intragastric acidity: 300 mg ranitidine b.d., 20 mg omeprazole o.m., 40 mg omeprazole o.m. vs. placebo

Background: There is considerable controversy about the degree of acid suppression that is optimal for the treatment of peptic disorders. Aim: To compare the effects of three different regimens that are reported to strongly inhibit acid secretion. Methods: Intragastric 24-hour pH monitoring was performed in 11 healthy subjects in a randomized, multiple, cross-over, double-blind study. Each subject received four dose regimens, each for 2 weeks, in a random order. The regimens were: 300 mg ranitidine b.d., 20 mg omeprazole o.m., 40 mg omeprazole o.m., and placebo. Results: The decrease in gastric acidity during the daytime and during the total 24-hour period by all three treatments was significantly greater than after placebo: a significant difference in acid inhibition was found between ranitidine and 40 mg omeprazole, but not between ranitidine and 20 mg omeprazole, nor between the two doses of omeprazole. During the night-time the decrease in gastric acidity by all three treatments was significantly greater than after placebo: no difference was seen between the two doses of omeprazole and ranitidine. For the time of pH greater than 3 we found no statistical difference between the various acid decreasing regimens. The pH remained significantly longer above 4 after ranitidine and the two doses of omeprazole compared with placebo, and also longer above 4 after 40 mg omeprazole compared with ranitidine, but not after 20 mg omeprazole compared with ranitidine, nor after the two different doses of omeprazole. Conclusions: Dosing with 300 mg ranitidine b.d., 20 mg omeprazole or 40 mg omeprazole is superior in gastric acid inhibition compared with placebo, when measured using 24-hour pH monitoring.     

Twenty-four-hour intragastric acidity and plasma gastrin concentration before and during treatment with either ranitidine or omeprazole

Simultaneous 24-hour intragastric acidity and plasma gastrin concentrations were measured in 12 duodenal ulcer patients before and on the twenty-eighth day of treatment with either ranitidine 150 mg b.d. or omeprazole 20 mg o.m. Median integrated 24-hour intragastric acidity was decreased significantly from 1148 to 490 and 36 mmol.hour litre-1 during treatment with ranitidine and omeprazole, respectively, whilst median intragastric 24-hour plasma gastrin was raised significantly from 328 to 799 and 1519 pmol.hour litre-1 respectively. When the results of all 48 experiments were considered together, there was a significant inverse correlation between the 24-hour integrated values for intragastric acidity and plasma gastrin concentration. Both drugs caused a significant elevation of plasma gastrin throughout the 24 hours, although ranitidine had no effect on intragastric acidity from 1900 to 2200 hours. When compared with similar profiles of acidity and gastrin in pernicious-anaemia patients, the modest elevations of plasma gastrin observed in this study suggest that neither drug will be associated with clinically relevant enterochromaffin-like cell proliferation in duodenal ulcer patients.     

Twenty-four-hour intragastric acidity and plasma gastrin concentration in healthy subjects and patients with duodenal or gastric ulcer, or pernicious anaemia

Twenty-four-hour intragastric acidity and plasma gastrin concentration were measured in healthy subjects (n = 16), and patients with duodenal (n = 12) or gastric (n = 10) ulceration, or pernicious anaemia (n = 8). Median integrated 24-hour intragastric acidity was highest in duodenal ulcer patients and lowest in pernicious anaemia patients (1148 and 0 mmol.hour litre-1, respectively). Median integrated 24-hour plasma gastrin was highest in pernicious anaemia and lowest in the healthy subjects (9886 and 238 pmol.hour litre-1, respectively). Pernicious anaemia patients have unremitting hypergastrinaemia throughout the 24 hours. The results of this study not only provide a reference range of acidity and plasma gastrin in health and disease, but also will act as a baseline for future studies using antisecretory drugs.     

Peptic ulcer in the elderly—a double-blind, short-term study comparing nizatidine 300 mg with ranitidine 300 mg

This was a randomized, double-blind, multicentre, short-term study comparing ranitidine and nizatidine at the standard dosages of 300 mg at bedtime. In 49 centres in Italy, all peptic ulcer patients aged over 65 years and with endoscopically documented acute disease were considered eligible for the study. Clinical check-ups were repeated every 3 weeks, while the endoscopic and biochemical assessments were scheduled at 6 and (in unhealed patients) 12 weeks. Statistics: chi-squared test, Fisher's exact test, Student t-test for unpaired data. The study included 170 duodenal ulcer and 75 gastric ulcer patients. Of these, 83/17 duodenal ulcer and 38/75 gastric ulcer patients were treated with nizatidine 300 mg and the remainder with ranitidine 300 mg. The groups were well-matched for common clinical data. Eight patients dropped out. Healing rates at 6 and 12 weeks were 81.9% and 91.5% for nizatidine-treated duodenal ulcer patients versus 78.1% and 94.2% for ranitidinetreated duodenal ulcer cases (P: N.S.); 6 and 12-week healing rates were 76.3% and 89.5% for nizatidinetreated gastric ulcer patients versus 67.6% and 83.8% for ranitidine-treated gastric ulcer patients (P: N.S.). No slow healing risk factors were found. Only minor adverse events were registered. In conclusion: ranitidine 300 mg and nizatidine 300 mg both proved effective and safe in the treatment of acute peptic ulceration in the elderly.     

Effect of omeprazole on intragastric and duodenal bulb acidity in duodenal ulcer patients

Intraluminal pH was measured simultaneously in the stomach and duodenal bulb with six small, glass electrodes tied together at 1.5-cm intervals. Ten patients with duodenal ulcer disease were studied under fasting conditions and for 3 h after a standard liquid meal on three occasions: day 1, before treatment; day 8, when the proton pump blocker omeprazole had been taken in a daily dose of 30 mg for 7 days consecutively, including the day of the pH study; day 9, 24 h after the last dose of omeprazole. Mean hydrogen ion activity and the percentage of time with pH below 3 was calculated from the digital pH data sampled at a frequency of 1 per second from each electrode. On day 8, five of the patients were permanently anacidic (pH greater than 4) in the stomach and duodenum, while the food-stimulation broke off anacidity for shorter periods in the other five patients. The pH pattern in the duodenal bulb was markedly altered in all patients with disappearance of the typical pH fluctuations, and a decrease in the time that the pH was below 3 from a median value of 30% before treatment to 0% in seven patients and close to 0% in three patients. On day 9, a large patient-to-patient variation was observed in gastric pH: three patients were still anacidic, four were markedly suppressed, but three patients reached near pre-treatment acidity. Duodenal bulb acidity was still decreased significantly on day 9 in all patients, with post-prandial pH below 3 for less than 5% of the time, compared with 30% before treatment.     

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.     

The effects of omeprazole 20 and 40 mg twice daily on intragastric acidity in duodenal ulcer patients.

BACKGROUND: The combination of omeprazole with amoxycillin or clarithromycin is used as treatment against Helicobacter pylori. It seems likely that the antibacterial activity of the antibiotic may be improved by increasing gastric pH towards neutrality, and a twice daily regimen of omeprazole is probably needed. AIM: To assess the effects of twice daily administration of omeprazole 20 and 40 mg. METHODS: Twelve duodenal ulcer patients in remission were randomized to receive in single-blind fashion either placebo, omeprazole 20 mg or omeprazole 40 mg twice daily (08.00 and 20.00 h). On the sixth day of dosing they underwent 24-h gastric pH-metry. RESULTS: Omeprazole 20 and 40 mg b.d. produced marked decreases (P < 0.001) of 24-h gastric acidity (pH 5.4 +/- 0.9 and pH 5.7 +/- 0.6, respectively, vs. a basal pH of 1.4 +/- 0.2) and kept gastric pH at levels higher than 3.0 for almost 24 h. Gastric pH was kept above 5.0 for about 18 h and above 6.0 for about 10 h, while the time spent above 7.0 did not exceed 3 h. There were no significant differences between the two omeprazole dosages at any pH threshold. CONCLUSION: Omeprazole 20 mg b.d. is sufficient to render the gastric milieu as anacidic as possible in duodenal patients.     

Acute treatment of reflux oesophagitis: a multicentre study to compare 150 mg ranitidine twice daily with 300 mg ranitidine at bedtime

A randomized, double-blind, clinical trial was undertaken to compare 150 mg ranitidine b.d. with 300 mg ranitidine nocte in the treatment of reflux oesophagitis. Endoscopy data were evaluable for 336 patients after 8 weeks of treatment. At this time 75% of patients who received 150 mg ranitidine b.d., and 73% of those who received 300 mg nocte, had healed or showed endoscopic improvement to grade I oesophagitis. At 12 weeks these rates had increased to 89 and 88%, respectively. Oesophageal biopsies from 258 patients at 8 weeks showed histological improvement in 44 and 47% of those treated with 150 mg ranitidine b.d. and 300 mg ranitidine nocte, respectively. After 12 weeks histological improvement was apparent in 57 and 54% of biopsies from each group, respectively. Symptom severity and frequency was reduced to a similar extent by both treatments. Adverse events were reported by 15 patients. A 300-mg bedtime dose of ranitidine was found to be a well-tolerated, effective alternative to twice daily treatment in reflux oesophagitis.     

The eflects of 300 mg ranitidine at night, twice daily and four times daily on intragastric acidity in normal subjects

The aim of this study was to compare to placebo the effects of 300 mg ranitidine nocte, b.d. and q.d. on intragastric acidity. The study was performed on healthy male subjects and intragastric acidity measured by radiotelemetry. All active treatments significantly decreased 24-hr acidity, with a median suppression of 61.0% with 300 mg ranitidine nocte, 77.7% with 300 mg b.d. and 78.0% with 300 mg q.d.s. There was no significant difference between the effects of two higher dose regimens: although the 300 mg q.d.s. suppressed daytime acidity more than 300 mg b.d. (88.9%vs. 77.8%), it suppressed nocturnal acidity less effectively (65.5%) than either 300 mg nocte (92.9%) or 300 mg b.d. (90.0%). These data suggest that only modest additional therapeutic acid inhibition can be achieved by increasing the dose of ranitidine above 600 mg daily.     

A comparison of low-dose maintenance treatment with enprostil against ranitidine in the prevention of duodenal ulcer recurrence

Enprostil, a prostaglandin E2 analogue, is effective in healing acute duodenal ulcer but its value in preventing recurrence, when given daily for maintenance therapy, is uncertain. In this three-centre study we compared enprostil and ranitidine maintenance therapy; the latter is known to reduce duodenal ulcer relapse rates. Patients whose duodenal ulcers had been healed by treatment with an H2-receptor antagonist were randomized to receive single-blind treatment with either 35 micrograms enprostil (n = 64) or 150 mg ranitidine (n = 64) at bedtime for periods of up to 1 year. Endoscopy was routinely performed at 3 months at one centre, and at 6 and 12 months at all three centres, or whenever ulcer symptoms recurred. Clinical assessment and laboratory investigations were performed every 3 months. Relapse, defined as recurrent ulcer with or without pain, or erosions with pain, was significantly greater in patients on enprostil, the comparative rates at 3, 6 and 12 months were: enprostil 23, 31 and 36% ranitidine 6, 12 and 17% (P = 0.013; P = 0.03 and P = 0.03, respectively). Thirty-one patients reported adverse events, the most common being headache (enprostil = 6, ranitidine = 2) and mild diarrhoea (enprostil = 6, ranitidine = 0). Four patients on enprostil were withdrawn for adverse events, although none terminated because of diarrhoea. There were no clinically significant changes in haematology or biochemistry. Enprostil may reduce duodenal ulcer relapse but at a dose of 35 micrograms nightly, it is less effective than 150 mg ranitidine nightly.     

Influence of the timing of administration of 300 mg ranitidine on 24-hour gastvic pH in patients with acute duodenal ulcer

The 24-hour intragastric pH of 12 patients with an acute duodenal ulcer was recorded with the aim of comparing the effects of two different times of administration of 300 mg ranitidine: post evening meal, or bedtime. This double-blind crossover trial involved 3 centres. Twenty-four-hour gastric pH was measured under standard conditions (meals, time schedule) at the middle of each 14-day treatment period. The analysis was performed on the percentage of times spent at pH levels below 1.5, 2, 3 and 4 for different periods and for the total 24 hours. During the whole day and night combined, as well as during the afternoon (12.00 hours-19.00 hours), there was no difference between the 2 regimens regardless of the pH profile studied. During the morning (07.30 hours-12.00 hours), the time spent below pH 1.5 and 2 was less when the drug was taken at bedtime (P less than 0.05). In contrast, during the whole night (19.00 hours-07.30 hours) the percentage of time spent below pH 1.5, 2 and 3 was significantly less when the drug was taken at post evening meal (P less than 0.05). These results show that in patients with acute duodenal ulcer, 300 mg ranitidine administered at the end of the evening meal provides better control of nocturnal acidity than administration at bedtime and hence is suggested for optimization of therapeutic efficacy.     

Double-blind, randomized trial of roxatidine 150 mg in the early evening versus bedtime administration in the short-term treatment of duodenal ulcer

Aim: To compare the efficacy and tolerability of early evening (19.00–21.00 hours) vs. bedtime (22.00–00.00 hours) oral administration of roxatidine 150 mg in the short-term treatment of active duodenal ulcer. Methods: The trial was randomized, double-blind and double-dummy, with parallel groups. A total of 276 patients were recruited and randomly assigned either to roxatidine in the early evening (n= 139) or roxatidine at bedtime (n= 137). Results: After 4 weeks, 78% of patients receiving roxatidine in the early evening and 74% of those treated at bedtime had achieved complete healing, as determined by per-protocol analysis. With intention-to-treat analysis the healing rates were 70.5% and 70.8%, respectively. After 8 weeks the healing rates in the early evening and bedtime treatment groups were 92% and 95% (per-protocol analysis) and 78% and 84% (intention-to-treat analysis). Both treatments proved effective in reducing the frequency and severity of daytime and nocturnal epigastric pain, as well as other ulcer-related symptoms. Conclusions: This study confirmed the healing and analgesic properties of roxatidine in duodenal ulcer disease. Early evening or bedtime dosing with roxatidine 150 mg resulted in similar 4- to 8-week rates of duodenal ulcer healing.     

Comparison between single morning and bedtime doses of 40 mg famotidine for the treatment of duodenal ulcer

The aim of this study was to compare the duodenal ulcer healing effects of morning (08.00 hours) vs. single bedtime (22.00 hours) doses of 40 mg famotidine, bearing in mind that the known efficacy of bedtime doses of H2-antagonists is regarded as evidence of the predominance of nocturnal gastric acidity in the pathogenesis of duodenal ulcer. This randomized double-blind multicentre trial was conducted in a total of 127 patients with endoscopically proven active duodenal ulcer. Nine patients dropped out and thus 118 were included in the final analysis. The duration of treatment was 4 weeks, and this was extended to 8 weeks in patients whose ulcers failed to heal by week 4. The patients in the two treatment groups were well matched for age and sex. The therapeutic efficacy parameters were endoscopic healing of the ulcer lesion and disappearance of pain. Results were compared using the chi-square method. The 4- and 8-week (cumulative) ulcer healing rates in the patients treated with the morning dose of famotidine were 77.2% and 86%, respectively, compared with 78.6% and 91.8% in those who received the bedtime dose. The differences failed to prove statistically significant either at week 4 (P = 0.85) or at week 8 (P = 0.31). The percentages of patients with ulcer pain, evaluated weekly, were similar in the two treatment groups. The equivalent efficacy of the morning and bedtime famotidine regimens raises doubts concerning the predominance of nocturnal gastric acidity in the pathogenesis of duodenal ulcer.     

Twenty-four-hour intragastric acidity and plasma gastrin during 3-month treatment with omeprazole in healthy subjects

Background : Prolonged treatment with omeprazole 20 or 40 mg/day is sometimes required, especially for severe oesophagitis. However, information about long-term effects on intragastric acidity and plasma gastrin response with such drug regimens is scarce.
Methods : Sixteen healthy subjects (11 men, 5 women, mean age 29 years) randomly received either 20 or 40 mg of omeprazole once daily (at 08.00 h) for 3 months. Gastric pH was recorded every 6 s for 24 h from noon to noon under standardized conditions, and blood samples were collected hourly in order to determine the 24-h plasma gastrin response on day 0 (pre-entry), day 7, day 28 and day 90.
Results : From day 0 to day 7, 24-h median pH increased from 1.7 to 4.6 and mean percentage of time at pH < 4 decreased from 89% to 35% with omeprazole 20 mg. Respective values with omeprazole 40 mg were 1.9 to 4.3, and 89% to 34%. Inhibition of gastric acidity remained unchanged during the 3 months of treatment. Despite similar effects on the basis of 24-h analysis, the decrease in daytime acidity was slightly higher with omeprazole 40 mg than with omeprazole 20 mg. Twenty-four-hour integrated plasma gastrin significantly increased with both drug regimens between day 0 and day 7 ( P  < 0.01), and between day 7 and day 28 ( P  < 0.01) with omeprazole 40 mg; there was no significant increase between day 28 and day 90 with either of the drug regimens.
Conclusion : Omeprazole 20 and 40 mg/day provides long-term stable acid suppression with a progressive increase in gastrin response, stabilizing after 2 months of treatment.     

Post-prandial intragastric and duodenal acidity are increased in patients with chronic pancreatitis

OBJECTIVES: Patients with chronic pancreatitis and exocrine insufficiency have lower intraduodenal pH compared to controls. It has been assumed that abnormal low intraduodenal pH in these patients not only results from impaired pancreatic bicarbonate secretion but also from an increased gastric acid load to the duodenum. METHODS: We have tested this hypothesis by combined intragastric and intraduodenal 24 h pH monitoring in nine chronic pancreatitis patients with exocrine pancreatic insufficiency and nine healthy control subjects during standardized test conditions. Postprandial gastrin and cholecystokinin release were also determined. RESULTS: Median 24-h intraduodenal pH (5.90 vs. 6.00) and intragastric pH (1.60 vs. 1.70) were not significantly different between patients and controls. However, in the 2-h postprandial periods intraduodenal pH was below five for a significantly higher percentage of time in chronic pancreatitis patients compared to controls (lunch: 14.5% vs. 0.17%, P=0.011; dinner: 24.1% vs. 5.75%, P=0.05). The post-dinner intragastric pH was below three for a significantly higher percentage of time in chronic pancreatitis patients vs. controls (72.2 vs. 48.9%, P=0.04). Postprandial gastrin release was not significantly different between the two groups. Postprandial secretion of cholecystokinin (CCK), as enterogastrone, was significantly (P < 0.01) reduced in chronic pancreatitis patients (78 +/- 13 pmol/L, 120 min) compared to controls (155 +/- 14 pmol/L, 120 min). CONCLUSIONS: Median intraduodenal and intragastric pH are not significantly decreased in patients with chronic pancreatitis and exocrine insufficiency but the postprandial time with an acidic pH in the duodenum (pH < 5) and in the stomach (pH < 3) is significantly (P 相似文献