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Biomedical subjects

J G Mills

Publications and source records attributed to J G Mills.

At least 19 recordsLinked to original sources
PubMed2000

A double-blind, randomized, placebo-controlled dose-ranging study to evaluate the efficacy of alosetron in the treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome is a common gastrointestinal disorder characterized by abdominal pain and discomfort and altered bowel habit. Antagonism at the 5-HT3 receptor may be of benefit in the treatment of irritable bowel syndrome. AIMS: To evaluate the effect of 12 weeks of treatment with alosetron, a 5-HT3 receptor antagonist at doses of 0.1 mg b.d., 0.5 mg b.d. and 2 mg b.d. in irritable bowel syndrome patients. METHODS: A double-blind, placebo-controlled, parallel-group study with a 2-week screening and a 12-week treatment period was conducted. A total of 462 patients (335 female) recorded details of the severity of their abdominal pain, and bowel function daily on a diary card throughout the study. At monthly clinic visits patients recorded the severity of their abdominal pain/discomfort and diarrhoea on a visual analogue scale. RESULTS: In the total population and in the female subpopulation (but not in males) alosetron 2 mg b.d. significantly increased the proportion of pain-free days and decreased the visual analogue scale score for diarrhoea compared with placebo. Alosetron at doses of 0.5 mg b.d. and 2 mg b.d. led to a significant hardening of stool, and a reduction in stool frequency in the total population. CONCLUSION: Alosetron at a dose of 2 mg b.d. is an effective treatment for female patients with irritable bowel syndrome.

Adolescent↗
PubMed1999

Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients.

BACKGROUND: Irritable bowel syndrome is one of the most common gastrointestinal disorders, yet no therapy convincingly controls the multiple symptoms of this syndrome. AIM: To compare the efficacy and tolerability of the new 5-HT3-receptor antagonist alosetron and the smooth muscle relaxant mebeverine in a double-blind, multicentre, randomized trial. METHODS: Six hundred and twenty-three nonconstipated females with irritable bowel syndrome were randomized to receive alosetron 1 mg twice daily (n=319) or mebeverine 135 mg three times daily (n=304) for 12 weeks, followed by a 4-week post-treatment period. The primary efficacy end-point was monthly responders for adequate relief of irritable bowel syndrome related abdominal pain and discomfort (defined as patients reporting adequate relief on at least 2 out of 4 weeks). Secondary end-points included assessments of bowel function, including urgency, stool frequency and stool consistency. RESULTS: There were significantly more responders in the alosetron group compared with mebeverine at months 2 and 3 (P < 0.01). Compared with mebeverine, the alosetron group experienced significant decreases in proportion of days with urgency and mean stool frequency, and had firmer stools within 1 week of starting treatment. A similar proportion of patients reported adverse events in the two treatment groups. CONCLUSIONS: In nonconstipated female irritable bowel syndrome patients, alosetron is significantly more effective than mebeverine in improving symptoms.

Adolescent↗
PubMed1999

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↗
PubMed1998

A prospective randomised controlled study of the use of ranitidine in patients with gastric cancer. Yorkshire GI Tumour Group.

BACKGROUND: Does the use of the histamine H2 receptor antagonist ranitidine improve the outcome of patients with gastric cancer? PATIENTS: A total of 222 patients with gastric cancer who had received radical or palliative resection or who were deemed inoperable at presentation. SETTING: Hospitals within Yorkshire, the participating clinicians being members of the Yorkshire GI Tumour Group. METHODS: A multicentre prospective randomised double blind trial comparing ranitidine 150 mg twice daily with placebo twice daily was undertaken. The principal outcome measures were survival and survival excluding those who died within 30 days of operation. RESULTS: The median survival (95% confidence intervals) was 331 (232 to 393) days for patients in the ranitidine group compared with 187 (143 to 269) for those in the placebo group. The difference in survival was not statistically significant (p = 0.225). When patients who died within 30 days of operation were excluded (21 in the placebo group, 15 in the ranitidine group), the difference in survival remained not significant (p = 0.358). No subgroup could be identified who significantly benefited from treatment, but for patients with stage VIa cancer the median survival was 134 days with placebo compared with 313 days with ranitidine (p = 0.073). CONCLUSION: This study does not show significant benefit from the use of ranitidine for gastric cancer but further larger studies may be indicated.

Adult↗
PubMed1997

Inhibition of intragastric acidity in healthy subjects dosed with ranitidine 75 mg: a comparative study with cimetidine and placebo.

BACKGROUND: Despite the widespread use of over-the-counter H2-receptor antagonists little is known about their duration of action on human gastric acid secretion. There are studies reporting inhibitory effects for up to 9 h post-dose but few data beyond this period. METHODS: Profiles of 20-h intragastric acidity were measured simultaneously in 24 healthy subjects who were dosed (at 12.30 h) with either ranitidine 75 mg, cimetidine 200 mg or placebo in a three-way crossover study, according to a standard protocol. Five-millilitre aliquots of gastric juice were aspirated half-hourly during the day (0-10 h post-dose) and hourly overnight (10-20 h post-dose). pH was measured to three decimal places with a glass electrode. Weighted intragastric acidity (AUC/time) was calculated for both day- and night-times using 2.5-h intervals during the day and 5-h intervals at night. Statistical analysis was by ANOVA. RESULTS: The results are expressed as mean weighted intragastric acidity (mmol/L). (i) Daytime (0-10 h post-dose): when dosed with placebo the weighted intragastric acidity was 31.03, decreasing to 10.37 (P < 0.001 vs. placebo) and 16.23 (P < 0.001 vs. placebo) when treated with ranitidine and cimetidine, respectively. Ranitidine inhibited weighted intragastric acidity to a greater degree than cimetidine (P < 0.001) during this period. (ii) Night-time (10-20 h post-dose): when dosed with placebo the weighted intragastric acidity was 21.36 decreasing to 16.65 (P < 0.001 vs. placebo) when dosed with ranitidine and remaining unchanged at 20.03 (P = 0.886 vs. placebo) when dosed with cimetidine. Ranitidine inhibited weighted intragastric acidity to a greater degree than cimetidine (P = 0.010) during this period. A sub-analysis of the two 5-h intervals showed that compared to placebo, ranitidine inhibited weighted intragastric acidity significantly in the 10-15 h period. However, its effect in the 15-20 h period did not differ from placebo. CONCLUSIONS: In healthy subjects, the inhibitory effect of ranitidine 75 mg on intragastric acidity can be detected 10-15 h after an oral dose. By contrast, the inhibitory effect of cimetidine 200 mg seems to be restricted to the first 10 h.

Adult↗
PubMed1997

The safety of ranitidine in over a decade of use.

BACKGROUND: Ranitidine hydrochloride (Zantac) is one of the most extensively studied and widely used drugs of all time. This has provided an excellent opportunity to define its safety profile. METHODS: Data from 189 controlled clinical trials in which more than 26,000 patients received daily doses of ranitidine for 4 weeks or more were reviewed. More than 80% of patients were treated with up to 300 mg ranitidine daily; the remaining patients received doses of up to 1200 mg daily. Eighty-seven trials were placebo controlled. Analyses of post-marketing surveillance and a database of all spontaneously reported adverse events were also evaluated. RESULTS: Overall in the clinical trial programme adverse events were reported by 20% of those receiving ranitidine compared with 27% of those receiving placebo. The pattern of events was similar in all treatment groups with no evidence of dose-related toxicity in regimens encompassing an eightfold range of therapeutic doses. Similarly in a programme of studies designed to evaluate a dose of ranitidine of 75 mg for non-prescription (over-the-counter) use in the treatment of heartburn, ranitidine was not associated with an adverse event profile distinct from that of placebo. Analysis of spontaneously reported adverse event data allowed identification of rare idiosyncratic events. CONCLUSIONS: Review of data from a large population of controlled clinical trials with analyses of postmarketing surveillance studies and spontaneously reported adverse events confirmed the excellent safety profile of ranitidine.

Anti-Ulcer Agents↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1995

Treatment of nonsteroidal anti-inflammatory drug-associated gastric and duodenal damage. Efficacy of antisecretory drugs and mucosal protective compounds.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of treatment for rheumatic diseases. However, a significant number of patients receiving these drugs experience upper gastrointestinal side effects, including physical injury to the gastroduodenal mucosa. This may range from clinically insignificant bleeding and minor erosive changes to deeper ulceration, with attendant risk of haemorrhage or perforation. The majority of the published literature concerning healing of NSAID-associated peptic ulcer with antisecretory drugs involves studies of the use of the H2-receptor antagonists, ranitidine and cimetidine. Peptic ulcers associated with NSAID use can be healed with these H2-receptor antagonists using the same doses as those used for healing of idiopathic gastric or duodenal ulceration. Most ulcers heal within 4-8 weeks in those patients who are able to discontinue their anti-inflammatory therapy. If the NSAID is continued, healing may be slightly delayed. At present, limited data only are available with respect to the use of the proton pump inhibitor, omeprazole, and no firm conclusions can be drawn regarding the use of the prostaglandin analogue, misoprostol, for the healing of NSAID-associated peptic ulceration.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Combination of ranitidine and cisapride in the treatment of reflux oesophagitis.

OBJECTIVE: To compare the efficacy of treatment for 8 or 12 weeks with a combination of 150 mg ranitidine twice daily plus 20 mg cisapride twice daily with ranitidine 150 mg twice daily alone in patients with moderate-to-severe reflux oesophagitis. DESIGN: A double-blind, randomized, parallel-group clinical trial. SETTING: Forty-two out-patient centres in the UK, Germany, Ireland, Denmark and South Africa. PATIENTS: A total of 344 symptomatic patients with endoscopically confirmed reflux oesophagitis (Hetzel grade 3 or 4) were randomly assigned to receive the study medication. INTERVENTIONS: Patients underwent a follow-up endoscopy after 8 weeks' treatment. Healing was defined as Hetzel grade 0 or 1 upon endoscopy. Patients with unhealed oesophagitis continued their allocated treatment regimen for a further 4 weeks before undergoing a repeat endoscopy. MAIN OUTCOME MEASURES: The primary efficacy analysis was based on a comparison of 12-week cumulative healing rates between the two groups. RESULTS: A statistically significant difference (P = 0.015) in the cumulative healing rate was observed between patients given ranitidine plus cisapride (82%) and those given ranitidine alone (71%). Oesophagitis in patients who received the combination was twice as likely to heal as that in patients who received ranitidine alone. CONCLUSION: A combination of 150 mg ranitidine twice daily and 20 mg cisapride twice daily is a safe and effective treatment for moderate-to-severe reflux oesophagitis and offers increased efficacy over ranitidine alone.

Administration, Oral↗
PubMed1993

Early evening dosing of ranitidine. Comparison with nighttime dosing of ranitidine or cimetidine in duodenal ulceration.

A double-blind multinational comparison of ranitidine 300 mg post evening meal (pem), ranitidine 300 mg nocte and cimetidine 800 mg nocte has been carried out in 1677 patients with endoscopically verified duodenal ulcer disease. Fifty-three percent of ulers healed by two weeks during treatment with ranitidine 300 mg pem and 88% by four weeks, while the results for ranitidine 300 mg nocte were 50% and 86%, respectively, and 44% and 84% for cimetidine. The difference between ranitidine 300 mg pem and cimetidine was significant at two weeks (P = 0.002, Mantel-Haenszel chi-squared test). The relative efficacy of the treatments was not dependent upon gender, smoking habit, alcohol intake, or ulcer frequency. However, the overall differences in healing between patients with small and large ulcers and patients with single and multiple ulcers were significantly different at weeks 2 and 4 (P < 0.001). Significantly more patients treated with ranitidine (60%) had complete relief of epigastric pain than those treated with cimetidine (54%) (P < 0.05). A meta-analysis of the four double-blind comparisons of ranitidine 300 mg pem (N = 841) and 300 mg nocte (N = 849), including the present study, failed to show the benefits of pem dosing, predicted from pharmacological studies.

Adult↗
PubMed1993

Association of age with the efficacy and safety of ranitidine and cimetidine in acute duodenal ulcer disease.

This multinational double-blind trial compared the efficacy and safety of ranitidine 300 mg nocte, 300 mg post-evening meal (pem) and cimetidine 800 mg nocte in patients with endoscopically verified duodenal ulcer disease aged < 60 years (n = 1318) and > or = 60 years (n = 354). The relative efficacy of the treatments was not dependent upon age after either 2 or 4 weeks of therapy. However, ulcer healing after 2 weeks of therapy was significantly higher in patients receiving ranitidine 300 mg pem than in those receiving cimetidine (p = 0.003) in the < 60-year group, but the difference was not significant in the > or = 60-year group. Fewer patients aged > or = 60 years on cimetidine (62%) became pain free compared with those on ranitidine (72% in both groups). Relief of epigastric pain and heartburn was related to pre-trial severity in both age groups. The incidence and type of adverse events were similar in the two age groups. It is concluded that ranitidine and cimetidine are as effective at healing duodenal ulcer and relieving ulcer symptoms in elderly as in younger patients.

Adolescent↗
PubMed1993

Does co-prescription of sucralfate with ranitidine therapy enhance the healing of gastric ulcers?

It has been suggested that the co-administration of ranitidine and sucralfate may enhance peptic ulcer healing more than administration of either drug alone. This study compared the frequency of healing of gastric ulcers treated with either ranitidine 300 mg nocte plus sucralfate 1 g tds or with ranitidine 300 mg nocte plus placebo. Patients (n = 259) were treated initially for 4 wk, and this period was extended to 8 wk for those patients whose ulcers had not healed. Ulcer healing and patient symptom data were assessed at 4 and 8 wk, whereas patients recorded the presence of ulcer pain on a daily basis. Ulcer healing rates were 63% and 66% at 4 wk, and were 93% and 91% at 8 wk, in the ranitidine-plus-sucralfate group and the ranitidine-plus-placebo group, respectively. Both treatments were equally effective in relieving symptoms. Thus, combination therapy with sucralfate provided no additional benefit over treatment with ranitidine alone.

Drug Administration Schedule↗
PubMed1991

Ranitidine in the treatment of duodenal ulcer disease: relationship between antisecretory effect and ulcer healing rate.

The relationship between drug-induced suppression of intragastric acidity and the rate of duodenal ulcer healing was examined using data for a single drug, ranitidine, from 156 clinical trials involving 16,362 patients together with data on acid suppression from 37 studies of intragastric acidity in 630 subjects. In these studies ranitidine was given in doses ranging from 150 mg to 1200 mg per day administered in 9 different dosage regimens. The overall percentage of patients whose duodenal ulcers healed at 2 and 4 weeks on the different regimens was highly correlated with the percentage suppression of 24-hour intragastric acidity induced by different regimens. Thus the therapeutic benefit of a given ranitidine dosage regimen in healing duodenal ulcers relates directly to its antisecretory effect.

Drug Administration Schedule↗
PubMed1989

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.

Adult↗
PubMed1989

Acute treatment of reflux oesophagitis: a multicentre trial to compare 150 mg ranitidine b.d. with 300 mg ranitidine q.d.s.

H2-receptor antagonists administered in conventional dosage regimens fail to heal a significant proportion of patients with moderate or severe reflux oesophagitis. We have compared the effects of a higher dose of ranitidine (300 mg q.d.s.) with the currently recommended dosage regimen (150 mg b.d.) in 138 patients suffering from reflux oesophagitis. After 4 weeks of treatment 29% of patients who received 150 mg ranitidine b.d., and 63% of patients who received 300 mg ranitidine q.d.s. had complete endoscopic healing of their lesions (P less than 0.0001). After 8 weeks these proportions had increased to 54% and 75%, respectively (P less than 0.01). After 4 weeks of treatment, compete symptomatic relief had been achieved in 46% of patients who received 150 mg ranitidine b.d. and in 67% of patients who received 300 mg ranitidine q.d.s. (P less than 0.05). After 8 weeks these proportions were 64% and 84%, respectively (P less than 0.05). Both dosage schedules were well-tolerated. We conclude that more rapid symptom relief and healing in reflux oesophagitis can be achieved with 300 mg ranitidine q.d.s. than with 150 mg ranitidine b.d.

Acute Disease↗
PubMed1989

Geographical differences of gastric ulcer healing rate in patients treated with ranitidine or placebo.

The literature was searched for clinical trials evaluating the use of 300 mg ranitidine daily in the acute treatment of gastric ulcer. All available trials were examined, and the results compared between countries to determine the extent of any geographical variation in ulcer healing rates. Published placebo studies in gastric ulcer were also reviewed for comparison. Sixty-six publications were inspected to determine the trial design, country of origin, gastric ulcer healing rates, determined endoscopically, and details of patient demography. Overall worldwide healing rates for ranitidine treatment were 63% at week 4 and 86% at week 8 (n = 2349 and 2256 respectively), compared with 34% at week 4 and 52% at week 8 for placebo (n = 790 and 231 respectively). Statistically significant differences were found between the healing rates for individual countries at week 4 (P less than 0.001) and week 8 (P less than 0.001). However, after exclusion of the results from Japan (35%, n = 278) and Yugoslavia (97%, n = 32) at week 4, and from Japan (80%, n = 467) and France (65%, n = 52) at week 8, the healing rates from the remaining countries were not statistically different from one another. The limited data available in relation to age, sex and smoking habits, or placebo healing rates contributed little to explaining these aberrant results. It is concluded that there is variation in gastric ulcer healing rates between countries, but only results from Japan seem to be out of line with the rest of the world.

Cimetidine↗