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  • 1
    Electronic Resource
    Electronic Resource
    Ranitidine, 75 mg, over-the-counter dose: pharmacokinetic and pharmacodynamic effects in children with symptoms of gastro-oesophageal reflux (2002)
    Oxford UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 16 (2002), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The use of over-the-counter antacids has increased in children under the age of 12 years, and has been followed by an apparent increase in the use of over-the-counter histamine-2 receptor antagonists. However, the pharmacokinetic and pharmacodynamic effects of over-the-counter histamine-2 receptor antagonists in the paediatric population are largely unknown.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To evaluate the pharmacokinetics and pharmacodynamics of a single dose of the over-the-counter histamine-2 receptor antagonist, ranitidine, 75 mg, in children with symptoms of gastro-oesophageal reflux disease.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Children aged between 4 and 11 years with symptoms of heartburn suspected to be due to gastro-oesophageal reflux disease were recruited at six clinical centres. Following a single dose of either oral ranitidine, 75 mg (n=19), or placebo (n=10), recording of intragastric pH and serial blood sampling were carried out for 6 h.〈section xml:id="abs1-4"〉〈title type="main"〉Results:The estimated pharmacokinetic parameters of ranitidine, 75 mg, were as follows: the median Cmax value of 477 ng/mL occurred within a median of 2.5 h after dosing, and the median half-life was 2.0 h. The intragastric pH began to rise approximately 30 min after dosing with ranitidine to a peak of pH ˜ 4. The pH in the ranitidine group remained higher than that in the placebo group throughout the 6-h evaluation period. Adverse events were generally mild.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Ranitidine, 75 mg, significantly increased the intragastric pH in children aged 4–11 years. The pharmacokinetic and pharmacodynamic profiles were similar to those in adults. Ranitidine, 75 mg, appears to be effective for the control of intragastric acidity for 5–6 h in children aged 4–11 years.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2002.01243.x
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  • 2
    Electronic Resource
    Electronic Resource
    A single dose of ranitidine 150 mg modulates oesophageal acid sensitivity in patients with functional heartburn (2004)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 20 (2004), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : The rapid onset and symptomatic response to histamine-2 receptor antagonists prior to the pharmacological effect on acid secretion suggests a different mechanism of action.Aim : To determine if ranitidine decreases oesophageal sensitivity to chemical and mechanical stimulation, potentially via oesophageal histamine receptors.Methods : A total of 18 patients with functional heartburn received oral ranitidine 150 mg b.d. or placebo for 7 consecutive days in a double-blind randomized crossover design and underwent Barostat balloon distention and Bernstein acid infusion on study day 1 (90 min postdose) and study day 7. First sensation and pain were recorded and pain severity was rated on a 5-point Likert scale and a 100 mm visual analogue scale. Least square mean values were generated and one-tailed t-tests were performed.Results : After a single dose of ranitidine 150 mg, time to pain with oesophageal acid infusion was increased by 29% (P 〈 0.05) and visual analogue scale and Likert scores were decreased by 20% (P 〈 0.06) and 23% (P 〈 0.02), respectively compared with placebo. After 1 week of ranitidine, positive alterations in sensory parameters persisted. Balloon distention sensory parameters were not altered by ranitidine.Conclusions : Ranitidine significantly decreased oesophageal sensitivity to acid. Failure of ranitidine to improve balloon sensory parameters supports existence of multiple sensory pathways in the oesophagus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.2004.02217.x
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  • 3
    Electronic Resource
    Electronic Resource
    Determination of the time of onset of action of ranitidine and famotidine on intra-gastric acidity (2002)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 16 (2002), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : No standard methods exist for determining the onset of action of gastric antisecretory agents in human subjects.Methods : Intragastric pH was measured when placebo, ranitidine 150 mg, ranitidine 75 mg or famotidine 10 mg were administered 30 min after the end of a meal.Results : When the onset of action was defined as the earliest time that mean gastric pH with active treatment was statistically significantly higher (P 〈 0.05) than the corresponding placebo value, the onsets of action of ranitidine 75 mg and 150 mg were 55 min, and of famotidine 10 mg, 90 min. When onset was defined in terms of a particular decrease in gastric acid concentration for the group as a whole or for individual subjects, there was an important variation in the relative times of onset of ranitidine 75 mg and famotidine 10 mg.Conclusions : When administered after a meal, the onset of action of ranitidine and famotidine on gastric pH can be determined for individual subjects as well as for the group as a whole. When onset was determined for the group using statistical significance, which does not depend on arbitrary cut-off points, ranitidine 75 mg had an earlier onset of action than did famotidine 10 mg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2002.01291.x
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of antacid formulation on postprandial oesophageal acidity in patients with a history of episodic heartburn (2002)
    Oxford UK : Blackwell Science Ltd.
    Alimentary pharmacology & therapeutics 16 (2002), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Heartburn self-treatment with antacids is extremely common. If the oesophagus is the primary site of antacid action, chewable antacids might raise the oesophageal pH more effectively than swallowable tablets.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To establish a model to assess postprandial acid reflux and to compare the onset and duration of action on oesophageal pH of different antacid formulations.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Twenty subjects with a history of episodic heartburn underwent eight pH monitoring sessions each for 5.5 h postprandially. One hour after consuming a meal consisting of chilli, cheese, raw onions and cola, subjects received 750 mg, 1500 mg and 3000 mg of either chewable or swallowable CaCO3 tablets, an effervescent bicarbonate solution or placebo. Oesophageal and gastric pH data were collected.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Mean intra-oesophageal pH remained lower than baseline for more than 1 h (pH range 5–5.5) postprandially, indicating reflux of somewhat acidic intragastric contents into the oesophagus. The onset of action on oesophageal pH was similar for all antacids (30–35 min). The duration of action on pH varied: chewable tablets and effervescent bicarbonate had relatively long durations of action (oesophagus, 40–45 min; stomach, 100–180 min); swallowable tablets had little effect.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:The meal model used in this study dependably produced acidic gastro-oesophageal reflux. Antacids increased oesophageal pH independent of gastric pH, demonstrating that chewing antacids controls oesophageal acidity more effectively than swallowing antacid tablets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2002.01178.x
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  • 5
    Electronic Resource
    Electronic Resource
    Effects of ranitidine bismuth citrate on gastric acid secretion and gastrin release in subjects with and without Helicobacter pylori infection (1996)
    Oxford BSL : Blackwell Science
    Alimentary pharmacology & therapeutics 10 (1996), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Ranitidine bismuth citrate is a novel antiulcerant that provides the antisecretory activity of ranitidine and the gastric mucosal protection and antibacterial properties of bismuth. Methods: This randomized, double-blind, placebo-controlled study evaluated the effects of single doses of ranitidine bismuth citrate 200 mg, 400 mg and 800 mg and ranitidine hydrochloride 150 mg on gastrin release and suppression of gastric acid secretion, and compared acid secretory profiles and gastrin release between Helicobacter pylori-negative and-positive patients. Plasma gastrin concentrations were determined by radioimmunoassay under basal conditions and in response to peptone meal stimulation. Acid secretion was measured under basal conditions and in response to peptone meal stimulation. Presence of H. pylori was determined by both 14C-urea breath test and ELISA serology. Results: Inhibition of gastric acid output by ranitidine bismuth citrate was both time- and dose-dependent over the 9-h post-dose study period. Doses of ranitidine bismuth citrate 400 mg and ranitidine hydrochloride 150 mg, which are equimolar, produced similar suppression of acid output regardless of H. pylori status. Ranitidine bismuth citrate had no effect on plasma gastrin concentrations regardless of H. pylori status. All doses of ranitidine bismuth citrate were well tolerated. Conclusions: Ranitidine bismuth citrate caused time-and dose-dependent reductions in meal-stimulated and between-meal gastric acid output regardless of H. pylori status. The magnitude of decreased acid secretion was similar with ranitidine bismuth citrate 400 mg and ranitidine hydrochloride 150 mg. Ranitidine bismuth citrate had no effect on plasma gastrin concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.1996.83255000.x
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  • 6
    Electronic Resource
    Electronic Resource
    Synergy between low-dose ranitidine and antacid in decreasing gastric and oesophageal acidity and relieving meal-induced heartburn (2001)
    Oxford UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 15 (2001), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The pathophysiology of recurrent postprandial heartburn and the basis for the effectiveness of antacids or low doses of histamine H2-receptor antagonists have not been well studied.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:The selected subjects (n=26) had heartburn more than four times a week for at least 2 months, which was responsive to antacids. Gastric pH and oesophageal pH were measured for 1 h before, during, and 4.5 h after ingestion of a meal over 0.5 h. Heartburn severity was assessed at 15-min intervals beginning at the end of the meal. Each subject randomly received placebo, 75 mg ranitidine, 420 mg calcium carbonate, and ranitidine plus calcium carbonate. Values for pH were converted to acid concentration (mM) and integrated acidity was calculated from the cumulative, time-weighted means of the acid concentrations for every second of the postprandial recording period.〈section xml:id="abs1-3"〉〈title type="main"〉Results:There was a close temporal relationship between heartburn and oesophageal acidity. Most oesophageal acid exposure occurred over a 90-min period that began approximately 45 min after the end of the meal. During this period the gastric acid concentration was less than 5% of maximal. Ranitidine significantly decreased gastric but not oesophageal acidity, whilst antacid significantly decreased oesophageal but not gastric acidity. Ranitidine plus antacid significantly decreased both gastric and oesophageal acidity. Antacid alone and ranitidine plus antacid significantly decreased heartburn severity.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:Determining integrated gastric and oesophageal acidity provides novel information regarding the pathophysiology of meal-induced heartburn as well as the actions of low-dose ranitidine and antacid. For subjects with meal-induced heartburn, treatment with low-dose ranitidine plus antacid is particularly effective in decreasing gastric and oesophageal acidity as well as heartburn severity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2001.01058.x
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  • 7
    Electronic Resource
    Electronic Resource
    Effect of selective 5HT3 antagonist (GR 38032F) on small intestinal transit and release of gastrointestinal peptides (1989)
    Springer
    Digestive diseases and sciences 34 (1989), S. 1511-1515 
    Details
    ISSN: 1573-2568
    Keywords: 5-hydroxytryptamine ; intestinal peptides ; small bowel transit ; motility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Antagonists of 5-hydroxytryptamine type 3 (5HT3) receptors reduce the nausea induced by cisplatinum, but the effects of these agents on 5HT3 receptors in the human gut remain to be defined. We examined the actions of one of these drugs (Glaxo GR 38032F) on small intestinal transit and mouth-to-cecum transit times in healthy man. We also quantified its effects on the release of peptide YY (PYY), neurotensin, human pancreatic polypeptide, gastrin-cholecystokinin, and motilin. Ten healthy volunteers were enrolled in a randomized, double-blind, placebo-controlled crossover study. Following a single intravenous dose of GR 38032F (0.15 mg/kg), we measured the time to appearance in plasma of sulfapyridine after injection of salicylazosulfapyridine into the duodenum. This was used as a measure of duodenocecal transit. The appearance of hydrogen in breath after ingestion of a meal containing lactulose was also correspondingly used to quantify the mouth-to-cecum transit of the “head” of the meal. Gastrointestinal hormones were assayed in plasma by specific RIAs; samples were drawn fasting (10 min after injection) and after breakfast (358 calories: 15.7 g protein, 55.4 g carbohydrate, 8.1 g fat). The postprandial integrated response and peak release of PYY was decreased by GR 38032F. There was also a trend for the peak release of neurotensin to be reduced. GR 38032F did not significantly alter small intestinal transit times or mouth-to-cecum transit times. We conclude that GR 38032F does not have a major effect on small intestinal transit in health.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01537102
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  • 8
    Electronic Resource
    Electronic Resource
    GR 38032F (Ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man (1990)
    Springer
    Digestive diseases and sciences 35 (1990), S. 477-480 
    Details
    ISSN: 1573-2568
    Keywords: colonic transit ; gastrointestinal peptides ; 5HT3 antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The newly recognized class of 5-hydroxytryptamine receptors (5HT3) may be involved in the induction of nausea, since their pharmacological antagonists are effective against emesis induced by chemotherapy. 5HT3 receptors are present on enteric neurons, and 5HT3 blockers may produce mild constipation; we thus hypothesized that 5HT3 receptors would modulate colonic motility. To determine if GR 38032F, a selective 5HT3 antagonist known to have antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18–70 years of age. On a standard 25-g fiber diet, 16 mg of GR 38032F was given orally thrice daily. Gastrointestinal peptides (peptide YY, human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on GR 38032F it was 39.1 hr (P〈0.0005). Transit times through the left colon (P〈0.0005) and rectosigmoid (P〈0.05) were prolonged by the drug, but right colonic transit was not significantly altered. Transit times did not correlate with age or gender, but subjects with shorter transit times were significantly more affected than were those with longer transit times. The peak release of peptide YY was minimally decreased following GR 38032F (P〈0.01), but the peak and integrated postprandial responses of human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, and substance P were not significantly altered by the drug. We conclude that 5HT3 receptors may be involved in the regulation of colonic transit in healthy man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01536922
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