Histamine H2-antagonists modify gastric emptying in the rat.

1 Histamine H2-receptor antagonists were tested for their effect on gastric emptying in the rat. 2 At low doses all the compounds were inactive except for burimamide which delayed and ranitidine which accelerated gastric emptying. 3 At high doses burimamide, metiamide, cimetidine and oxmetidine delayed, whereas ranitidine accelerated gastric emptying; tiotidine remained ineffective. 4 Changes in emptying rate were not accompanied by changes in emptying pattern which, with all the compounds examined, proceeded, as in the controls, by apparent first order kinetics. 5 The mechanism of the ranitidine-induced acceleration of gastric emptying seemed to be connected with an interference with the cholinergic system, whereas the mechanism of cimetidine- and oxmetidine-induced slowing of gastric emptying was apparently related to cholinolytic and possibly also relaxant effects of the compounds. 6 These different effects of the various H2-blockers are consistent with the idea that changes in emptying rate are independent of H2-receptor blockade.     

A comparative study of the effect of cimetidine and ranitidine on the rate of gastric emptying of liquid and solid test meals in man

Paired studies were carried out on 18 healthy male volunteers (20.9 +/- 1.9 years; mean +/- S.D.) to compare the effect of oral doses of the H2-receptor antagonists, ranitidine and cimetidine, on the rate of gastric emptying of radiolabelled solid and liquid test meals. Oral administration of ranitidine 300 mg accelerated the emptying of a liquid meal from the stomach, but it had no significant effect on the rate of emptying of a solid meal. Oral administration of either 400 or 800 mg cimetidine did not alter the rate of emptying of either the liquid or the solid meals from the stomach.     

A comparison of gastric emptying rate after cimetidine and ranitidine measured by applied potential tomography.

Gastric emptying was measured using applied potential tomography (APT) after crossover administration of 800 mg cimetidine and 300 mg ranitidine orally. Ten volunteers were studied, each on two occasions. Two hours after taking ranitidine or cimetidine, the volunteer was given a liquid and gastric emptying was measured over 60 min. There was a small but statistically significant delay in gastric emptying following ranitidine compared with cimetidine (P less than 0.04). The median (range) time to 50% emptying (t50) was 24 (15-60) min after ranitidine compared with 22 (15-46) min after cimetidine.     

Cimetidine versus ranitidine: single-dose, oral regimen for reducing gastric acidity and volume in ambulatory surgery patients

This placebo-controlled trial compared the efficacy of single oral doses of cimetidine or ranitidine in maintaining intragastric pH and volume greater than 2.5 and less than 25 ml, respectively, in ambulatory surgery patients requiring general anesthesia. Patients were randomized to receive either placebo, ranitidine HCl 150 mg, or cimetidine HCl 400 mg upon rising on the morning of surgery. At induction, the cimetidine and ranitidine groups had significantly higher (p less than 0.05) gastric pH values than the placebo group. At extubation, the ranitidine group had a significantly higher (p less than 0.05) gastric pH than either the cimetidine or placebo group. Both H2-blocker groups had lower volumes when compared with the placebo group at extubation (p less than 0.05). There were more patients at risk for aspiration pneumonitis (pH less than 2.5 and/or volume greater than 25 ml) in the cimetidine group (46 percent) than in the ranitidine group (15 percent). All placebo-treated patients were at risk for aspiration pneumonitis. We did not find subjective clinical evidence of aspiration pneumonitis in our patients. We conclude that both ranitidine and cimetidine are superior to placebo, but ranitidine may be the preferred agent because of its more consistent effect on gastric pH and volume.     

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.     

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.     

Cimetidine, ranitidine and mifentidine in specific gastric and duodenal ulcer models

The protective effect of cimetidine, ranitidine and a newer H2-receptor antagonist, mifentidine (proposed INN), on models of gastric and duodenal damage, caused by activation of H2 receptors, was studied. Gastric erosions were induced in rats by intravenous dimaprit (100 mg/kg) while duodenal damage was investigated in guinea pigs following subcutaneous administration of dimaprit (2 mg/kg, 6 doses). All the compounds reduced or abolished gastric and duodenal damage in rats and guinea pigs, mifentidine being more potent than both cimetidine and ranitidine. The antiulcer effect of the H2-receptor antagonists was related to the dose and to their ability to inhibit dimaprit-induced gastric acid secretion. The duration of action proved to be different for the three compounds. According to the two dosing schedules adopted to evaluate the duration of action, mifentidine, compared to cimetidine and ranitidine, required considerably lower oral dosages to display its protective effect.     

Ranitidine: a new H2-receptor antagonist

The pharmacology, pharmacokinetics, clinical efficacy, adverse reactions, drug interactions, and dosage of ranitidine are reviewed; specific comparisons are made of this new H2-receptor antagonist with the older agent, cimetidine. Ranitidine is a potent inhibitor of gastric acid secretion whose chemical structure lacks the imidazole group previously believed to be essential for H2-receptor blocking activity. The new agent does not bind substantially to the cytochrome P-450 mixed-function oxidase system and does not penetrate the cerebrospinal fluid appreciably. Peak serum ranitidine concentrations occur within one to two hours after oral administration; approximately 50% of an oral dose reaches systemic circulation. There are at least three metabolites of ranitidine, but substantial fractions of both i.v. and oral doses are recovered unchanged in the urine. Ranitidine's duration of action is 8-12 hours. Controlled clinical trials have shown ranitidine to be effective in the treatment of duodenal and gastric ulcers, Zollinger-Ellison syndrome, and prophylaxis against aspiration during anesthesia. Ranitidine has been effective in patients unresponsive to or intolerant of cimetidine. In clinical trials, the incidence of adverse effects from ranitidine has been low; certain rare but serious side effects that have been noted with cimetidine have not been associated with ranitidine therapy. There is no evidence thus far that certain drug-drug interactions observed with cimetidine therapy will occur with ranitidine. Oral adult daily doses of ranitidine are likely to be 300 mg given as the hydrochloride salt in two divided doses. Ranitidine is similar to cimetidine in efficacy but has an apparently safer adverse-effects profile. Ranitidine is likely to be the preferred agent in certain clinical situations.     

Antisecretory and antiulcer effect of the H2-receptor antagonist famotidine in the rat: comparison with ranitidine.

1 The effects of the new H2-receptor antagonist famotidine, administered orally, on gastric secretion and emptying as well as on experimentally-induced gastric and duodenal ulcers were studied in the rat. Ranitidine was used as a reference compound. 2 Both compounds inhibited acid secretion in a dose-dependent manner. Calculated ED50 values were 0.80 and 6.84 mg kg-1 for famotidine and ranitidine, respectively. However, the duration of the antisecretory action was the same for both drugs. 3 The effect of the two drugs, administered at equiactive antisecretory doses, on gastric emptying was different. Ranitidine significantly accelerated the emptying rate whereas famotidine had no effect. 4 Famotidine reduced, in a dose-dependent manner, ulcer incidence in stomachs of dimaprit-treated rats and in duodena of cysteamine-treated animals with a potency respectively 2 and 7 times higher than that of ranitidine. 5 Famotidine is therefore an effective antisecretory and untiulcer compound. Its potency, but not its efficacy, is higher than that of ranitidine. Moreover, the duration of the antisecretory action is virtually the same for both drugs.     

Gastroprokinetic activity of nizatidine during the digestive state in the dog and rat.

The present study was undertaken to clarify a prokinetic activity of nizatidine (CAS 76963-41-2) during the digestive state as well as gastric emptying of a solid test meal in comparison with cimetidine (CAS 51481-61-9), famotidine (CAS 76842-35-6) and cisapride (CAS 81098-60-4). Intravenous administration of nizatidine (0.3-3 mg/kg) enhanced the motility of the gastric antrum and duodenum during the digestive state. With cimetidine (1-10 mg/kg) and famotidine (0.1-1 mg/kg) enhancement of gastric motility was observed only with the highest dose of cimetidine, and famotidine had no effect. Marked enhancement of gastric motility was observed with cisapride (0.1-0.5 mg/kg). After intraduodenal administration of nizatidine (10 and 20 mg/kg) and cisapride (0.25 and 0.5 mg/kg), they also amplified the contractile activity of the gastric antrum. Gastric emptying of a solid test meal was accelerated by intraperitoneal administration of nizatidine (1-10 mg/kg) to the same extent as cisapride (0.1-1 mg/kg). In addition, even in a model of delayed gastric emptying induced by clonidine, nizatidine, like cisapride, improved the rate of gastric emptying. Neither cimetidine (3-30 mg/kg) nor famotidine (0.3-3 mg/kg) affected the gastric emptying of a solid meal or delayed gastric emptying. These results suggest that nizatidine enhanced gastric motility even during the digestive state, and accelerated gastric emptying of a solid meal, similar to cisapride. Furthermore, nizatidine improved clonidine-induced delayed gastric emptying. These prokinetic activities of nizatidine may by useful for the treatment of abdominal symptoms due to dysmotility and delayed gastric emptying in patients with gastritis and non-ulcer dyspepsia (NUD). In comparison with famotidine and cimetidine, nizatidine may be different from other histamine H2-receptor antagonists and has unique properties other than its gastric antisecretory activity.     

The effect of ranitidine on gastric acid secretory response curves to histamine, pentagastrin or bethanechol in the dog with a Heidenhain pouch

The H2-receptor antagonists ranitidine and cimetidine were tested against gastric secretory dose-response curves to histamine, pentagastrin and bethanechol in the Heidenhain-pouch dog. Histamine-induced gastric secretion was antagonized in a competitive manner by both ranitidine and cimetidine, but ranitidine was approximately 8 times more potent than cimetidine. Pentagastrin -induced secretion was markedly reduced by ranitidine and cimetidine but this antagonism was not competitive in nature. Bethanechol-induced gastric secretion was slightly reduced by both drugs. These findings are discussed in relation to the physiological control of gastric secretion.     

Antagonism of vasodepressor and gastric secretory responses to histamine by the H2-receptor antagonists, ranitidine and cimetidine, in the anaesthetized dog.

1 The new H2-receptor antagonist, ranitidine, has been compared with cimetidine as an inhibitor of gastric acid secretion in the anaesthetized dog. 2 Both ranitidine and cimetidine given intravenously inhibited histamine-induced gastric secretion in a dose-related manner. Ranitidine was 4.2 times more potent than cimetidine when given as an intravenous infusion and 9.6 times more potent as an intravenous bolus dose. 3 In a separate series of experiments, ranitidine was compared with cimetidine as an antagonist of vasodepressor responses to histamine. Mepyramine alone displaced the histamine dose-response curve to the right. After a maximally effective dose of mepyramine, further displacement could be achieved with ranitidine and cimetidine, ranitidine being 19.2 times more potent than cimetidine. 4 Ranitidine alone has no effect on vasodepressor response curves to histamine, acetylcholine or (-)-isoprenaline or on vasopressor response curves to phenylephrine. 5 These results indicate that displacement of the histamine dose-response curve after mepyramine blockade by ranitidine and cimetidine is due to selective H2-receptor antagonism.     

Intragastric pH monitoring in acute upper gastrointestinal bleeding and the effect of intravenous cimetidine and ranitidine

Intragastric pH was measured continuously from 1800 to 1200 hours the following day in 22 duodenal ulcer patients and in eight gastric ulcer patients, all of whom had been admitted as emergencies with acute upper gastrointestinal haemorrhage. The effects of intravenous cimetidine or ranitidine were compared with no treatment. In patients with duodenal ulcer, median intragastric pH was 1.8 (range 1.0-4.9) in the group receiving no treatment. In the cimetidine group (400 mg, 6-hourly, n = 8) median pH was 4.7 (range 1.5-7.7) and after ranitidine (50 mg, 6-hourly, n = 10) it was 3.8 (range 1.2-7.8). The pH remained above 4.0 for 67% of the recording time with cimetidine, 47% with ranitidine and for only 3% with placebo. Intragastric pH in gastric ulcer patients without treatment was higher (median 3.4, range 1.0-6.9) than in duodenal ulcer patients with treatment. Both H2 antagonists raised intragastric pH in patients with gastric ulcer and maintained a gastric pH of greater than 4.0 for at least 50% of the time. Presently recommended i.v. doses of cimetidine and ranitidine do not consistently maintain gastric pH above 4.0 for long periods in patients with peptic ulcer bleeding.     

Effect of histamine H2-receptor antagonists on acute inflammatory of the rat paw oedema

The effect of three histamine H2-antagonists, cimetidine, ranitidine, and loxtidine, on acute rat paw oedema induced by histamine, carrageenan or complete Freund's adjuvant, have been examined. Administered intraperitoneally, all three antagonists inhibited histamine-induced paw oedema dose-dependently in the range 0.5-15 mumol kg-1. The highest dose of cimetidine produced an inhibition of 92% as against 38% with the same dose of mepyramine. Analysis of the concentration-effect curves produced IC50 values of 1.66, 5.12 and 12.30 mumol kg-1 for cimetidine, loxtidine, and ranitidine, respectively, on histamine-induced oedema. In carrageenan-induced inflammation 12.3 mumol kg-1 of each of the three drugs produced significant inhibition, whereas in adjuvant-induced inflammation, (acute phase), cimetidine was very active, loxtidine less so and ranitidine inactive. Thus the relative effectiveness of the antagonists (cimetidine greater than loxtidine greater than ranitidine) appears to differ from their known potency relationship (loxtidine greater than ranitidine greater than cimetidine) on H2-mediated effects. We conclude that H2-receptors are involved in the induction of rat paw oedema, especially those induced by histamine and carrageenan, but that their relative effectiveness appears atypical.     

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.     

Comparative investigation of the influence of nizatidine, ranitidine, and cimetidine on the steady-state pharmacokinetics of theophylline in COPD patients.

The influence of usual regimens of the H2 blocking drugs, cimetidine, ranitidine, and nizatidine on the steady-state plasma concentrations and pharmacokinetic characteristics of theophylline was studied in seventeen patients with chronic obstructive pulmonary disease (COPD). Patients were dosed to steady-state with an oral, sustained-release formulation of theophylline given in therapeutic doses twice daily for 2 weeks. Over the next 4 weeks, each patient received a week-long regimen of each H2 blocker concomitantly with theophylline, and a week-long regimen of theophylline alone (control). At the end of each of the latter 4 weeks the steady-state pharmacokinetics of theophylline were assessed. Neither ranitidine nor nizatidine treatment altered the steady-state pharmacokinetics of theophylline relative to the control phase (i.e. no H2 blocker treatment). Values for theophylline C(ave), Cssmax, AUC0-12, and CLoral were significantly different during cimetidine treatment compared with all other treatments (ranitidine, nizatidine, and control). Cimetidine increased theophylline Cssmax, AUC0-12 and Cave by approximately 32%, and decreased theophylline oral clearance by approximately 23%. The authors conclude that cimetidine alters the steady-state pharmacokinetics of theophylline in COPD patients, whereas ranitidine and nizatidine are without effect.     

Enprostil. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of peptic ulcer disease

Enprostil, a synthetic analogue of prostaglandin E2, is effective in the treatment of patients with duodenal or gastric ulcers. As demonstrated in pharmacological studies in healthy volunteers and in patients with inactive ulcer disease, gastric acid secretion is suppressed by up to 80% for almost 12 hours after single doses of enprostil. The drug also reduces the secretion of pepsin, another 'aggressive' factor in peptic ulcer disease. Interestingly, in contrast to the H2-receptor antagonists, which either increase or have no effect on serum gastrin concentrations, enprostil inhibits basal and postprandial gastrin release. Although the possible effects of enprostil on 'defensive' factors in peptic ulcer disease-which are thought to protect the mucosa-require much further clarification, some evidence obtained in man indicates that bicarbonate secretion is enhanced by enprostil. Further, data from animal studies suggest that microvascular integrity may be preserved by a direct action of enprostil on the gastric mucosa. In healthy volunteers, the administration of enprostil in antisecretory doses protects the gastric mucosa against of enprostil in antisecretory doses protects the gastric mucosa against aspirin-induced injury. Cumulative rates of ulcer healing observed in patients with duodenal ulcers after 4 weeks' treatment with enprostil 35 micrograms twice daily were about 50 to 80%, which were similar to those seen in comparative trials with usual therapeutic doses of cimetidine or pirenzepine, but less than occurred with ranitidine. Moreover, enprostil has been shown to relieve daytime pain in a similar percentage of patients as do these H2-receptor antagonists, but night-time pain appears to respond less well to therapy with the prostaglandin. As evidenced by a few controlled trials in patients with gastric ulcers, treatment with enprostil 35 micrograms twice daily for 6 weeks provides ulcer healing in parallel with pain relief as effectively as cimetidine and ranitidine in a high percentage of patients (about 80% after 6 weeks). Prophylactic treatment with enprostil after initial ulcer healing has reduced the rate of duodenal ulcer relapse in patients 'at risk', but to a lesser extent than has ranitidine. Gastrointestinal symptoms-abdominal cramping and pain, flatulence, nausea and notably, diarrhoea-are the most frequently reported side effects during therapy with enprostil. Diarrhoea occurs in about 10% of patients, but is rarely of a severity necessitating treatment discontinuation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of the new anti-ulcer drug nizatidine on prostaglandins in the rat gastric mucosa.

The effects of nizatidine (N-[2-[[[2-[(dimethylamino)methyl]- 4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine , CAS 76963-41-2), a new histamine H2-receptor antagonist, on the content of prostaglandins (PGs) in the rat gastric mucosa at doses that inhibit basal gastric acid secretion were compared with those of two other histamine H2-receptor antagonists, cimetidine and ranitidine. Nizatidine did not inhibit basal gastric acid secretion at a dose of 0.4 mg/kg but showed dose-dependent inhibition at doses of 10, 30, and 100 mg/kg. This drug had no effects on the content of PG in the gastric mucosa when subcutaneously administered at doses of 0.4, 10, 30 and 100 mg/kg once daily for 5 days. Cimetidine and ranitidine administered at doses that markedly inhibit basal gastric acid secretion (250 and 100 mg/kg/d, respectively) had no effects on the content of PG in the gastric mucosa. On the other hand, nizatidine, cimetidine, or ranitidine at concentrations of 1-100 mumols/l did not inhibit in vitro PGE2 synthesis using sheep seminal vesicle microsomes. These results suggest that nizatidine did not affect in vitro PGE2 synthesis and even doses that markedly inhibit gastric acid secretion had no effects on the content of PGs in the gastric mucosa.     

Effect of domperidone on cimetidine and ranitidine absorption in rabbits

Cimetidine and ranitidine absorption were studied after oral administration to rabbits, alone or in combination with oral and intravenous domperidone. Blood samples were collected before and 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.5, and 6.0 h after cimetidine and ranitidine administration. Assays of cimetidine and ranitidine in plasma samples were carried out using HPLC method. Domperidone overall significantly reduced the area under the plasma concentration-time curve (AUC) by approximately 30 per cent for both drugs. However, domperidone had little effect on the maximum plasma concentration (Cmax), the time taken to reach the maximum plasma concentration (Tmax), and the elimination half-life (t1/2) of cimetidine and ranitidine. The results suggest that domperidone affects the extent but not the rate of cimetidine and ranitidine absorption by enhancing gastric emptying.     

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.