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Biomedical subjects

G A Pipkin

Publications and source records attributed to G A Pipkin.

9 recordsLinked to original sources

Onset of action of antisecretory drugs: beneficial effects of a rapid increase in intragastric pH in acid reflux disease.

BACKGROUND: The majority of patients who have symptomatic acid reflux disease will have a normal oesophageal mucosa or will have only a mild degree of oesophagitis. Treatment to relieve symptoms as they occur may be the best way to manage these patients, to whom the speed of symptom relief is of primary importance. The effervescent complex used to formulate effervescent ranitidine contains sodium bicarbonate and monosodium citrate, and has, therefore, an intrinsic acid-neutralizing capacity in addition to the well-documented antisecretory activity. METHODS: The results of studies of the effects of effervescent ranitidine tablets on intragastric pH and on the relief of heartburn are reviewed. RESULTS AND CONCLUSIONS: When compared with the standard ranitidine tablet, the effervescent formulation results in a significantly greater and more rapid rise in intragastric pH in the hour immediately after dosing. Comparative studies show that intragastric pH is raised significantly faster after a single dose of effervescent ranitidine than after a famotidine rapid release tablet and after either an omeprazole or a lansoprazole capsule. In patients with acid reflux disease, effervescent ranitidine provides quicker relief of symptoms than a standard tablet and is preferred by most patients for this reason. The majority of patients (more than 80%) report symptom relief within 60 min of taking effervescent ranitidine.

Gastric Acid↗

Review article: one-week clarithromycin triple therapy regimens for eradication of Helicobacter pylori.

BACKGROUND: One-week triple therapies have been endorsed as the treatment regimens of choice for eradication of Helicobacter pylori infection. Those that include clarithromycin appear to be the most effective. AIM: To review reports of triple therapies that include clarithromycin. METHODS: Reports were identified from the literature to May 1998. The variation between study designs prevents a formal meta-analysis. A measure of the relative efficacies of regimens has, however, been gained by comparison and by pooling of intention-to-treat eradication rates. RESULTS: One hundred and ninety-two studies were identified which included 264 treatment arms of a 1-week triple therapy composed of clarithromycin with amoxycillin or a nitroimidazole (metronidazole or tinidazole), and either ranitidine bismuth citrate or a proton pump inhibitor (omeprazole, lansoprazole or pantoprazole). From reports of these studies, an intention-to-treat H. pylori eradication rate could be determined from 210 treatment arms of 151 studies. CONCLUSIONS: There is little to choose between the efficacies of 1-week clarithromycin-based triple therapy eradication regimens. However, those comprising clarithromycin, a nitroimidazole and either ranitidine bismuth citrate or a high dose of omeprazole are, in general, the most effective. Against antibiotic-resistant strains of H. pylori, regimens including ranitidine bismuth citrate may be more effective than those including a proton pump inhibitor.

Anti-Bacterial Agents↗

High Helicobacter pylori eradication rate with a 1-week regimen containing ranitidine bismuth citrate.

BACKGROUND: High Helicobacter pylori eradication rates have consistently been reported with 2-week dual therapy regimens of ranitidine bismuth citrate plus clarithromycin. Ranitidine bismuth citrate with two antibiotics may provide an alternative 1-week eradication regimen. METHODS: This double-blind, randomized, parallel group, international, multicentre study compared ranitidine bismuth citrate 400 mg b.d. and clarithromycin 500 mg b.d. for 2 weeks (RC) with ranitidine bismuth citrate 400 mg b.d., clarithromycin 500 mg b.d. and metronidazole 400 mg b.d. for 1 week (RCM) for eradication of H. pylori in 350 patients with dyspepsia. RESULTS: Treatment with RC and RCM eradicated H. pylori (established by the combination of two negative results from two discrete 13C-UBTs at nominal weeks 4 and 12) from 89% (95% CI: 84-94) and 92% (95% CI: 88-97) of the observed population, and from 78% (95% CI: 72-84) and 80% (95% CI: 75-86) of the intention-to-treat population. When established only by one negative 13C-UBT result at least 28 days after the end of treatment, the respective intention-to-treat rates were 85% (95% CI: 79-90) and 88% (95% CI: 83-93). Both regimens were well-tolerated, only 6% of patients given RC and 4% given RCM discontinued treatment. Median plasma bismuth concentrations at the end of the second week of study were low, at 3.5 and 0.4 ng/ mL, respectively. CONCLUSIONS: Ranitidine bismuth citrate triple therapy for 1 week (RCM) and dual therapy for 2 weeks (RC) were equally effective for the eradication of H. pylori infection.

Anti-Bacterial Agents↗

New options in Helicobacter pylori eradication: efficacy, resistance and synergy.

The eradication of Helicobacter pylori has become the focus of much attention since the first attempts at developing effective therapies some 10 years ago. This review focuses on ranitidine bismuth citrate (RBC), the first new drug to be introduced for use in the eradication of H. pylori. RBC when combined with clarithromycin gives consistently high eradication rates (above 80% intention-to-treat assessment in double-blind, international studies) as a simple dual therapy for 14 days or when combined with two antibiotics as a triple therapy for 7 days. RBC enhances the in vitro killing of H. pylori by antibiotics, such as clarithromycin, metronidazole or tetracycline, in a synergistic manner. This effect is seen even when the H. pylori strains are 'resistant' to the antibiotics. Such a synergistic effect probably explains the increased efficacy of RBC-clarithromycin dual therapies compared with clarithromycin dosed with acid-suppressive agents such as H2-receptor antagonists or proton-pump inhibitors.

Anti-Bacterial Agents↗

Clarithromycin dual therapy regimens for eradication of Helicobacter pylori: a review.

BACKGROUND: Peptic ulcer disease can be cured by eradication of Helicobacter pylori during treatment to heal the ulcer. Dual therapy regimens were among the first to be granted approval for use. Reports of dual therapies including clarithromycin as the sole antibiotic are reviewed. METHODS: Reports were identified from literature up to May 1997. Information reviewed included patient population, medical diagnosis, trial design, eradication regimens, and H. pylori eradication rates. The great diversity between studies limits formal meta-analysis but a measure of relative efficacy has been obtained by comparison of eradication rates derived by clearly defined methods and by pooling data. RESULTS: Seventy-five reports of trials with 104 dual therapy treatment arms were reviewed. H. pylori eradication rates reported with ranitidine bismuth citrate plus clarithromycin range from 70-96% with a pooled observed rate of 85%. With omeprazole plus clarithromycin, reported eradication rates range from 27-90% with the pooled reported rate being 66%. Few data are available with either lansoprazole or ranitidine hydrochloride plus clarithromycin. CONCLUSION: High H. pylori eradication rates derived by consistent and clearly defined methods have been seen with ranitidine bismuth citrate plus clarithromycin. Lower and more variable rates are reported with clarithromycin and either a proton pump inhibitor or a histamine H2-receptor antagonist.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Ranitidine bismuth citrate plus clarithromycin for the eradication of H. pylori.

Reported observed intention-to-treat eradication rates for ranitidine bismuth citrate plus clarithromycin for 14 days range from 70-86% in studies from the USA and 82-96% in multinational studies carried out primarily in Europe. Two double-blind head-to-head comparisons with omeprazole plus clarithromycin or amoxycillin have shown that ranitidine bismuth citrate plus clarithromycin gives considerably higher eradication rates than the omeprazole based regimens. Ongoing studies will define the efficacy of shorter duration dual therapies and provide further data on two antibiotics with ranitidine bismuth citrate. The possibility that ranitidine bismuth citrate may help in the eradication of resistant organisms and even in the prevention of primary resistance requires further work to expand the preliminary in vitro observations. In the meantime, it can be concluded that ranitidine bismuth citrate, when used in conjunction with clarithromycin for 14 days, is an effective therapy for the eradication of H. pylori.

Anti-Bacterial Agents↗

The safety of ranitidine bismuth citrate in controlled clinical studies.

Ranitidine bismuth citrate (Pylorid, Tritec) is a novel drug which heals peptic ulcers and when co-prescribed with either clarithromycin or amoxycillin eradicatesHelicobacter pylori. In controlled clinical studies it was well-tolerated when given alone or when co-prescribed with either antibiotic. Data from 20 clinical studies are reported in this analysis of safety with almost 5000 patients having received ranitidine bismuth citrate (200, 400, or 800 mg twice daily). The incidence of adverse events reported with this new drug, either alone or with an antibiotic, was not different from or lower than in patients given placebo and was independent of the dose of ranitidine bismuth citrate tested. Most commonly reported events (>1% of patients) were upper respiratory tract infection, constipation, diarrhoea, nausea and vomiting, dizziness, and headache, the latter being the only event reported by >2% of patients who received ranitidine bismuth citrate alone. Adverse events considered by the clinical investigator to be adverse reactions occurred with a similar frequency amongst patients given ranitidine bismuth citrate (8%), ranitidine hydrochloride (6%), or placebo (6%). The incidence of adverse reactions was greater when co-prescribed with amoxycillin (11%) or clarithromycin (20%) although it was not different from that noted with the antibiotics alone. Serious adverse events were reported in similar proportions of patients given placebo, ranitidine bismuth citrate alone or with an antibiotic, and ranitidine hydrochloride (range: <1-2%). The safety profile of ranitidine bismuth citrate was thus comparable to that of ranitidine hydrochloride (Zantac), a drug with a well-established record of safety in clinical use.

Journal Article↗

Stress-related mucosal disease. Pathophysiology, prevention, and treatment.

The advent of gastrointestinal endoscopy has allowed us to follow the morphologic results of severe stress on the gastrointestinal mucosa. It has become clear, however, that the presence of mucosal abnormalities does not always correlate with the presence of overt bleeding, or with the effect of bleeding on the overall outcome of such patients. In fact, the incidence of severe gastrointestinal hemorrhage, secondary to stress-related mucosal disease, has been decreasing over the past decade, as the care of these critically ill patients has improved. In patients who do have overt hemorrhage, however, the mortality rate is extremely high. It therefore remains the duty of the clinician to identify patients who are at high risk of having overt hemorrhage, and ensure that they receive adequate prophylactic therapy.

Anti-Ulcer Agents↗

Does ranitidine affect blood alcohol concentrations?

No interaction occurs between ranitidine and alcohol when alcohol 0.3 g/kg or more is taken by either fed or fasted subjects. Ranitidine is associated with small increases (2-4 mg/dl) in blood alcohol concentrations in subjects given alcohol 0.15 g/kg under specific experimental conditions. Mean peak blood alcohol concentrations nevertheless remain low (< 20 mg/dl) after the amount, which is equivalent to about 3 oz of wine or 1 oz of 80-proof liquor. Such changes also occur when alcohol is ingested after different types of foods, and are smaller than the increases when it is drunk on an empty compared with a full stomach. The pharmacokinetic effect seen with ranitidine is without apparent clinical or social significance.

Alcohol Drinking↗