Famotidine. Pharmacodynamic and pharmacokinetic properties and a preliminary review of its therapeutic use in peptic ulcer disease and Zollinger-Ellison syndrome

Famotidine is a new histamine H2-receptor antagonist. On a weight basis, famotidine is 20 times more potent than cimetidine and 7.5 times more potent than ranitidine in inhibiting basal and pentagastrin-stimulated gastric acid secretion in humans. Therapeutic trials have shown that famotidine 20 mg twice daily or 40 mg at bedtime may be an effective alternative to standard doses of cimetidine for healing gastric ulcers and to standard doses of cimetidine and ranitidine for healing duodenal ulcers. When used prophylactically, a single 20 mg dose of famotidine at night decreases the incidence of duodenal ulcer recurrence (versus placebo). However, further study is needed to clarify the comparative efficacy of the H2-receptor antagonists, in particular as maintenance therapy for healed peptic ulcer. Preliminary results in a few patients with Zollinger-Ellison syndrome indicate that famotidine, alone or in combination with an anticholinergic agent, gives good control of gastric acid hyperacidity with no evidence of biochemical or haematological toxicity. Famotidine appears to be well tolerated. Unlike cimetidine, it does not have antiandrogenic effects or alter hepatic metabolism of drugs. However, wider clinical experience with famotidine is needed to accurately determine its relative tolerability compared with other anti-ulcer drugs. Thus, famotidine appears to be a suitable and well tolerated alternative to cimetidine and ranitidine for healing peptic ulcers, but wider clinical experience is needed to assess its relative efficacy and tolerability in the long term maintenance treatment of patients with healed ulcers as well as in patients with Zollinger-Ellison syndrome.     

法莫替丁治疗消化性溃疡

经胃镜证实活动性消化性溃疡用双盲对照法,23例(男21例,女2例,年龄41±11a)服法莫替丁20mg bid;另17例(男14例,女3例,年龄40±14a)服雷尼替丁150mg bid。十二指肠和胃溃疡分别于服药后4wk和6wk复查胃镜,结果法莫替丁显效率96％,雷尼替丁为94％,2组无显著差异。     

Effects of ranitidine on quality of gastric ulcer healing compared with famotidine: a randomized, controlled, multicenter trial

Ranitidine has been found to have anti-inflammatory action as well as antisecretory action in experimental models. However, there are no reports in human gastric ulcer. The aim of this study was to investigate the effects of ranitidine compared with those of famotidine on the quality of gastric ulcer healing. We randomly assigned 69 consecutive patients with gastric ulcers to ranitidine (n = 34) or famotidine (n = 35) for 12 weeks, with endoscopic assessment of the quality of gastric ulcer healing and histological assessment of gastric mucosa 12 weeks after treatment started. Ulcer healing rates of over 95% were very similar in the two groups. The rates of ulcer scars with a flat pattern (good-quality healing) were significantly higher in the ranitidine group than in the famotidine group (per protocol, 63.0% and 34.5%, p = 0.033). The neutrophil infiltration score in the body mucosa treated with famotidine, but not ranitidine, significantly increased after treatment. In contrast, the mononuclear cell infiltration score in the antral mucosa treated with ranitidine, but not in that treated with famotidine, had significantly decreased. In conclusion, initial therapy with ranitidine significantly improved the quality of gastric ulcer healing and the histological scores of gastric mucosa compared with famotidine.     

A controlled study of 20 mg famotidine nocte vs. 150 mg ranitidine nocte for the prevention of duodenal ulcer relapse

A 24-week, double-blind, randomized study at 13 centres compared the efficacy and safety of 20 mg famotidine nocte and 150 mg ranitidine h.s. for the prevention of duodenal ulcer recurrence. All participants had been successfully treated for an acute duodenal ulcer with 40 mg famotidine nocte. Patients were endoscoped at baseline and at 24 weeks, unless symptoms warranted earlier examination: of the 208 patients enrolled, 86 who received famotidine and 84 who received ranitidine met all protocol criteria and were considered evaluable. Intention to treat and per protocol analyses showed non-significant trends in favour of famotidine (P = 0.44 and 0.16, respectively). During the 24-week observation period, 16.3% of the famotidine group and 25% of the ranitidine group had an ulcer recurrence (95% CI of percentage difference -0.22 + 0.04). At 24 weeks, relief of day and night pain was reported by 81.2% and 91.8% of the famotidine-treated patients, respectively. The corresponding figures in the ranitidine group were 73.5% and 85.5%. No laboratory abnormalities related to the study-drugs were noted and only two drug related (possibly or probably) adverse experiences were reported, both in the famotidine group. The data from this study therefore, supports the conclusion that the efficacy of 20 mg famotidine nocte is comparable to that of ranitidine in preventing duodenal ulcer recurrence, with comparable tolerability for long-term therapy.     

Comparison of famotidine with cimetidine and ranitidine

The pharmacodynamic, therapeutic, and toxicologic properties of famotidine are evaluated and compared with those of cimetidine and ranitidine. Famotidine, an H2-receptor antagonist with a thiazole nucleus, is approximately 7.5 times more potent than ranitidine and 20 times more potent than cimetidine on an equimolar basis. Therapeutic trials indicate that famotidine 20 mg b.i.d. or 40 mg at bedtime is as effective as standard doses of cimetidine and ranitidine for healing duodenal ulcers. A dose of 40 mg at bedtime appears to heal benign gastric ulcers. A single nocturnal dose of 20 mg is effective in preventing duodenal ulcer relapse. Further studies are required that compare the efficacy of famotidine with cimetidine and ranitidine in the treatment of gastric ulcers and in the prevention of recurrent duodenal ulcers. The overall incidence of adverse effects observed with famotidine appears to be similar to that reported for cimetidine and ranitidine. Like ranitidine, famotidine does not have antiandrogenic effects or substantially inhibit the hepatic metabolism of drugs. Because of its increased antisecretory potency and lack of antiandrogenic effects at higher doses, famotidine may be the H2-receptor antagonist of choice in treating Zollinger-Ellison syndrome. Additional clinical experience, as well as cost and safety factors, will determine the place of famotidine in treating and preventing acid-peptic disorders.     

Famotidine. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in peptic ulcer disease and other allied diseases

Famotidine is a highly selective histamine H2-receptor antagonist. In healthy volunteers and patients with acid hypersecretory disease it is approximately 20 to 50 times more potent at inhibiting gastric acid secretion than cimetidine and 8 times more potent than ranitidine on a weight basis. As shown in placebo-controlled trials, famotidine is effective in healing both duodenal and gastric ulcers. Famotidine 20mg twice daily or 40mg at bedtime achieves healing rates and symptom relief similar or superior to those achieved by cimetidine 800mg daily or ranitidine 300mg daily in patients with peptic ulcer disease. Results of 1 placebo-controlled study suggest that famotidine prevents recurrence of duodenal ulcer, but comparative trials are needed to establish its relative efficacy in maintenance therapy. The few non-comparative trials conducted to date also suggest that famotidine 10 to 20mg twice daily may be effective in the treatment of gastritis and reflux gastro-oesophagitis. In comparative trials, famotidine was similar in efficacy to cimetidine in the treatment of upper gastrointestinal bleeding and to ranitidine in the prevention of pulmonary aspiration of acid. In patients with Zollinger-Ellison syndrome, the potency and long duration of action of famotidine may confer an advantage over other H2-receptor antagonists--in individualised doses (mean 0.33 g/day) famotidine successfully controlled acid secretion for up to 72 months in 1 study of such patients. Accumulated clinical evidence confirms that famotidine is very well tolerated and is free of the antiandrogenic effects infrequently reported with cimetidine. Moreover, famotidine is not associated with altered hepatic metabolism of drugs. Thus, famotidine is an effective, well-tolerated alternative to cimetidine and ranitidine. Famotidine is also promising as maintenance therapy for preventing recurrence of duodenal ulcer and as initial or maintenance treatment of gastric hypersecretory disorders, but further clinical experience, particularly in the long term, is needed to define the relative efficacy and tolerability of famotidine in these indications.     

Lafutidine can improve the quality of gastric ulcer healing in humans: a randomized, controlled, multicenter trial

Improving the quality of ulcer healing (QOUH) is one of the valid methods of prevention of relapse of gastric ulcers. We investigated the effect of lafutidine on the QOUH of gastric ulcer compared with famotidine in a randomized, multi-centre controlled trial. Consecutive 80 patients with a gastric ulcer were randomly assigned to receive twice daily either lafutidine (10 mg) or famotidine (20 mg) for 12 weeks. Esophagogastroduodenoscopy was performed to examine the ulcer healing rate and rate of fl at type ulcer scars using dye-contrast. The gastric ulcer healing rate was 92.1% in the lafutidine group (35/38) and 94.7% in the famotidine group (36/38). The rate of flat-type ulcer scars was significantly higher in the lafutidine group (68.4%, 26/38) than in the famotidine group (42.1%, 16/38) (P = 0.021). In conclusion, the present study demonstrated that lafutidine, as compared to famotidine, yields a signifi cantly superior QOUH in patients with gastric ulcers in the clinical setting. Received and accepted 3 August 2006     

Single night-time doses of 40 mg famotidine or 800 mg cimetidine in the treatment of duodenal ulcer

Famotidine (40 mg) and 800 mg cimetidine as single night-time doses were compared in a randomized, double-blind, multicentre study of acute treatment for duodenal ulceration. Fifteen centres recruited 304 patients into the study. Of these, 274 were included for analysis, with 136 receiving famotidine and 138 receiving cimetidine. After 4 weeks, 75% of the patients who received famotidine and 77% of the patients who received cimetidine were healed. At 6 weeks the cumulative healing rates were 91% with famotidine and 87% with cimetidine. Differences between the groups were not significant at 4 or 6 weeks. No significant difference in healing rates between smokers and non-smokers was found. Day and night pain resolved rapidly in both groups. Both treatments were well-tolerated; adverse events were reported in 17 patients on famotidine and 18 on cimetidine, with headache the most frequent event in both groups. Famotidine is effective and well-tolerated in the short-term treatment of duodenal ulcer.     

Ranitidine: a review of its pharmacology and therapeutic use in peptic ulcer disease and other allied diseases

Ranitidine is a new histamine H2-receptor antagonist which, unlike cimetidine, does not contain an imidazole group. On a weight basis, ranitidine is 4 to 10 times more potent than cimetidine in inhibiting stimulated gastric acid secretion in humans. Therapeutic trials comparing ranitidine and cimetidine have demonstrated that ranitidine 150 mg twice daily is an effective alternative to cimetidine 1000 mg daily in 4 divided doses in increasing the rate of healing of duodenal and gastric ulcers over a period of 4 to 6 weeks. Ranitidine, given as a single 150 mg dose at night, decreases the incidence of ulcer recurrence. Preliminary studies in the Zollinger-Ellison syndrome and in patients intolerant of, or unresponsive to cimetidine, indicate that ranitidine controls the gastric hyperacidity and heals most ulcers, including those which failed to respond to months of treatment with cimetidine 1 to 1.6 g daily. Ranitidine, unlike cimetidine, has no antiandrogenic effects and does not alter hepatic metabolism of drugs. Ranitidine is well tolerated. Preliminary reports of the resolution of cimetidine-induced adverse effects following substitution of ranitidine, suggest that ranitidine may be of value in patients intolerant of cimetidine. However, wider clinical experience with ranitidine is needed to determine the clinical relevance of these reports.     

High-dose ranitidine for the prevention of recurrent peptic ulcer disease in rheumatoid arthritis patients taking NSAIDs.

BACKGROUND: Continuous therapy with low-dose ranitidine (150 mg b.d.) is known to be effective for the prevention of recurrent nonsteroidal anti-inflammatory drug (NSAID)-associated duodenal ulcer but not for gastric ulcer. AIM: To investigate, in a double-blind placebo- controlled study, the preventive effect of a high dose of ranitidine (300 mg b.d.) on the recurrence of both duodenal ulcers and gastric ulcers in rheumatoid arthritis patients with a continuous need for NSAIDs. METHODS: Rheumatoid arthritis patients with a history of peptic ulcer disease were randomized to receive either ranitidine 300 mg b.d. or placebo for 12 months. Endoscopy was performed at study entry and after 6 and 12 months. End-point was the recurrence of gastric or duodenal ulcers. RESULTS: The study was stopped after a blinded interim analysis; at that time 10 of the 15 included patients in each treatment group were evaluable. Recurrent duodenal ulcers had occurred in four patients treated with placebo and none of the patients treated with ranitidine (Fisher's exact one-tailed P = 0.04; 95% CI, - 0.70 to - 0.10). Recurrent gastric ulcers had occurred in six patients in the placebo group and three patients in the ranitidine group (Fisher's exact one-tailed P = 0.18; 95% CI, -0.72 to 0.12). Two patients in the placebo group had developed both duodenal ulcers and gastric ulcers. No adverse events were observed. CONCLUSIONS: High dose ranitidine is effective for the prevention of recurrent duodenal ulcer but not for recurrent gastric ulcer in rheumatoid arthritis patients taking NSAIDs.     

Ranitidine. An updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in peptic ulcer disease and other allied diseases

Ranitidine, a histamine H2-receptor antagonist, is now well established as a potent inhibitor of gastric acid secretion effective in the treatment and prophylaxis of gastrointestinal lesions aggravated by gastric acid secretion. Therapeutic trials involving several thousands of patients with peptic ulcer disease confirm that ranitidine 300mg daily administered orally in single or divided doses is at least as effective as cimetidine 800 to 1000mg daily in increasing the rate of healing of duodenal and gastric ulcers. Similar dosages of ranitidine have been shown to relieve the symptoms of reflux oesophagitis and heal or prevent gastrointestinal damage caused by ulcerogenic drugs. Ranitidine 150mg orally at night maintains ulcer healing in the long term. Ranitidine has also demonstrated good results in the treatment of Zollinger-Ellison syndrome and in the prevention of aspiration pneumonitis when given prior to surgery and to pregnant women at full term. It may also have a place in the management of acute upper gastrointestinal bleeding and in the prevention of stress ulcers in the intensive care setting, although these areas require further investigation. Ranitidine has been used safely in obstetric patients during labour, in children, the elderly, and in patients with renal impairment when given in appropriate dosages. The drug is very well tolerated and is only infrequently associated with serious adverse reactions or clinically significant drug interactions. Even at high dosages, ranitidine appears devoid of antiandrogenic effects. Ranitidine is clearly comparable or superior to most other antiulcer agents in the treatment and prevention of a variety of gastrointestinal disorders associated with gastric acid secretion. With its favourable efficacy and tolerability profiles, ranitidine must be considered a first-line agent when suppression of gastric acid secretion is indicated.     

A multicentre, randomized, double-blind study comparing nocte famotidine or ranitidine for the treatment of active duodenal ulceration

The efficacy and safety of famotidine and ranitidine in the treatment of active duodenal ulcer were compared in a multicentre, randomized, double-blind study. The study was carried out in five centres which included a total of 143 patients with endoscopically documented active duodenal ulcer. The patients received either famotidine (one tablet of 40 mg at night) or ranitidine (two tablets of 150 mg at night). Endoscopic examinations were performed at 4 and 6 weeks of active treatment. Daytime and nocturnal pain were also monitored, and the laboratory and clinical profiles evaluated. One hundred and thirty-three patients fulfilled the evaluation criteria (66 patients in the famotidine group and 67 in the ranitidine group). Healing rates at 4 or 6 weeks of treatment showed no significant differences between the famotidine and ranitidine groups. The healing rates were 80% at week 4 and 97% at week 6 in the famotidine group, and 77% at week 4 and 96% at week 6 in the ranitidine group. Similar results were observed in both treatment groups with regard to pain resolution, decrease in antacid intake and safety profile.     

Can higher doses of an H2-receptor antagonist accelerate duodenal ulcer healing?

Drugs that inhibit gastric acid secretion heal duodenal ulcers at a rate that correlates with the ability of individual treatment regimens to decrease 24-h intragastric acidity. As current therapeutic regimens of ranitidine decrease 24-h intragastric acidity submaximally, higher dosages may expedite duodenal ulcer healing. To test this hypothesis a randomized, double-blind clinical trial was conducted in 245 patients with duodenal ulcer to compare the effects of standard dose (300 mg nocte) and high-dose (300 mg q.d.s.) ranitidine. Patients were assessed after 2 weeks of treatment and, if unhealed, after a further 2 weeks of therapy. The therapeutic gain in ulcer healing at the 2-week endoscopy of the higher dose over the lower dose of ranitidine was 22% (68% vs 46%, P less than 0.001). The cumulative ulcer healing rates at the 4-week endoscopy were 88% and 92% for the standard and high-dose ranitidine groups, respectively (N.S.). By 2 weeks, 61% of patients treated with standard ranitidine therapy and 79% of those receiving 300 mg ranitidine q.d.s. were pain-free (P less than 0.01). A further 2 weeks of therapy enabled 88% and 97% of patients (N.S.) to become pain-free on these two regimens, respectively. The drug regimens were equally well tolerated. Thus higher-dose ranitidine can significantly accelerate the healing of duodenal ulcer with improvement in pain relief.     

Controlled comparison of cimetidine and carbenoxolone sodium in gastric ulcer.

Fifty-four outpatients with endoscopically diagnosed benign gastric ulcer were allocated at random to treatment with either cimetidine 800 mg daily for six weeks or carbenoxolone sodium 300 mg daily for one week then 150 mg daily for five weeks. Ulcers were reassessed by endoscopy at the end of the trial. The endoscopist was unaware of the treatment and did not take part in the clinical care of the patients. Twenty-one of the 27 patients (78%) given cimetidine and 14 of the 27 (52%) given carbenoxolone had healed ulcers. Symptomatic response occurred earlier with cimetidine but was not significantly better. Unwanted effects were more common in the carbenoxolone group: 12 patients developed hypokalaemia, four of whom needed oral potassium supplements. The results suggest that histamine H2-receptor blockade is at least as effective as carbenoxolone sodium for benign gastric ulcer and produces fewer side effects.     

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 H2-receptor blockade by ranitidine on ulcer healing and gastric acid secretion in patients with gastric and duodenal ulcers

The effect of treatment for 4 weeks with the H2-receptor antagonist ranitidine 200 mg daily on ulcer healing, clinical symptoms and antacid consumption, and on gastric acid secretion, was studied in a double blind trial in 48 patients with a total of 50 endoscopically confirmed duodenal, prepyloric or corporeal gastric ulcer. Patients whose ulcers did not show complete healing within 28 days were continued openly on ranitidine for up to a further 4 weeks. Endoscopy, basal gastric acid secretion (BAO) and pentagastrin-stimulated maximal secretion (PAO) studies were performed at 2-week intervals. After four weeks, 73% of the gastro-duodenal ulcers in the ranitidine group showed complete healing versus 42% in the placebo group (p less than 0.05). Gastric acid secretion was considerably inhibited both under basal (89%; p less than 0.001) and maximal challenge (71%; p less than 0.001) conditions. The inhibitory effect was still pronounced 13-15 h after administration of ranitidine 100 mg. Symptoms and the need for antacids were significantly reduced. Ranitidine appears to be an efficacious, safe and well tolerated medicine principle for the treatment of gastro-duodenal ulcer disease.     

High quality of ulcer healing in rats by lafutidine, a new-type histamine H2-receptor antagonist: involvement of capsaicin-sensitive sensory neurons

This study was conducted to determine whether the low recurrence rate of ulcers after treatment with lafutidine, an antiulcer drug possessing both an antisecretory and gastroprotective activities, was mediated by capsaicin-sensitive sensory neurons (CSSN). Chronic gastric ulcers in rats were induced by serosa-searing. The ulcer healing and recurrence were evaluated by endoscopy. Drugs were orally administered. Desensitization of CSSN was induced by pretreatment with capsaicin. Lafutidine (30 mg/kg) accelerated the ulcer healing significantly, and the recurrence rate was much lower than that for the vehicular control. In CSSN-desensitized rats, lafutidine also accelerated the ulcer healing significantly, but the low recurrence rate shown in normal rats was counteracted. The recurrence rate of the combination of famotidine (30 mg/kg) and teprenone (100 mg/kg) was lower than that of famotidine alone. In conclusion, the low recurrence rate of ulcers after lafutidine treatment in rats seems to depend on the gastroprotective mechanisms involving CSSN.     

Comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of active gastric ulcer—a European multicentre study

Background:

Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active, benign gastric ulcers.

Methods:

In this randomized, double-blind, multicentre study, conducted at 25 European sites, rabeprazole and omeprazole were compared in patients with active gastric ulcers. Two hundred and twenty-seven patients with active benign gastric ulcer were randomized to receive either rabeprazole 20 mg (n = 113) or omeprazole 20 mg (n = 114) once daily for 3 or 6 weeks, with healing monitored by endoscopy.

Results:

After 3 weeks, complete healing (ITT analysis) was documented in 58% of patients given rabeprazole and 61% in patients given omeprazole (N.S.). After 6 weeks the healing rates were identical in both groups at 91%. Rabeprazole-treated patients had numerically greater symptom relief at all 12 points of comparison. The differences significantly favoured rabeprazole at week 3 for daytime pain improvement (P = 0.023) and at week 6 for pain frequency (P = 0.006) and complete resolution of night pain (P = 0.022). Both drugs were well-tolerated over the 6-week treatment course. Mean changes from baseline to end-point in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen.

Conclusion:

In this study, rabeprazole produced healing rates comparable to omeprazole at weeks 3 and 6, but provided more consistent and occasionally significantly superior symptom improvement. Both treatments were well-tolerated.

     

Omeprazole (20 mg o.m.) versus ranitidine (150 mg b.d.) in duodenal ulcer healing and pain relief

The object of this double-blind, multicentre study was to compare duodenal ulcer healing rates after 2 to 4 weeks of treatment with either 20 mg omeprazole o.m. or 150 mg ranitidine b.d. One hundred and eighty-one patients were randomized: 91 received omeprazole and 90 received ranitidine. In a per protocol analysis at 2 weeks, 63% of the patients were healed on omeprazole and 65% of the patients were healed on ranitidine (N.S.); at 4 weeks 91% were healed in the omeprazole group and 96% were healed in the ranitidine group. There were no differences in ulcer symptom relief between the two groups. There were no significant changes in laboratory values in either of the groups. Adverse events were few and mainly mild and transient. We conclude that both omeprazole (20 mg o.m.) and ranitidine (150 mg b.d.) result in rapid, ulcer healing rates.     

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.