Mifentidine represents a potential improvement in the class of H2-receptor antagonists because of its long plasma half-life (10 h). The aim of this study was to evaluate the effects of mifentidine on pentagastrin-induced gastric pepsin and acid secretion in man. Nine healthy subjects participated in two separate sessions in which they were given randomly either a single oral dose of placebo or 10 or 20 mg of mifentidine, in accordance with an incomplete balanced block design. Basal secretion was measured 30 min before the administration of the drug, and 90 min later unstimulated gastric secretion was collected through a nasogastric tube for an additional 30 min. Then, 2 μg/kg/h pentagastrin were infused intravenously for 2 h, and gastric juice collected again in 15-min aliquots. Acid output was almost completely blocked by both doses of mifentidine during the unstimulated period (-99%). Pentagastrin infusion induced 10 times as much acid output as in the unstimulated phase. This dramatic increase was reduced by 32% with the low dose of mifentidine and to a major extent (-86%) with the high dose. The pepsin output was significantly inhibited by both doses of mifentidine during unstimulated (-83% and -82%) and stimulated (-49% and -71%) phases. Acid output correlated with the area under the mifentidine plasma levels (r=-0.69, p < 0.05). It is concluded that mifentidine is a potent inhibitor of both acid and pepsin secretion in man.
The present study was designed to determine the effects of an antacid suspension containing magnesium hydroxide and aluminum hydroxide (30 ml of Maalox) on the oral bioavailability of rufloxacin (400 mg). Rufloxacin was administered orally to 12 healthy volunteers according to a randomized, balanced, crossover design. Three treatments were administered to each subject, with a 10-day washout period between treatments; the treatments included rufloxacin alone, rufloxacin taken 5 min after antacid, and rufloxacin taken 4 h before antacid. Administration of antacid within 5 min before the administration of rufloxacin resulted in a substantial decrease in rufloxacin absorption, with a mean percent relative bioavailability compared with control values of 64% (range, 42 to 77%). Administration of antacid 4 h after the administration of rufloxacin slightly affected the absorption of the quinolone (mean relative bioavailability, 87%; range, 51 to 110%). Antacids that contain magnesium and aluminum salts reduce the absorption of rufloxacin. The extent of this interaction depends on the time that elapses between administration of the two drugs.
The use of colloidal bismuth subcitrate (CBS) has been recently suggested for cimetidine-resistant duodenal ulcers. We have therefore compared the activity of CBS with that of two different doses of cimetidine in patients whose duodenal ulcers had not healed after 8 weeks of therapy with cimetidine, 1.2 g, or ranitidine, 300 mg/ day. Forty-three patients (35 men and 8 women) were randomly allocated to one of the following oral regimens: CBS, 120 mg 4 times a day, or cimetidine (C), 400 mg 3 times a day, or cimetidine, 400 mg at meals plus 800 mg at bedtime, for 4–8 weeks. The interim analysis after 4 weeks of treatment showed similar percentages of healing in the two cimetidine schedules (46.7% with C, 1.2g, and 42.9% with C, 2g, respectively); conversely, CBS treatment resulted in a significantly higher healing rate as compared with both C, 1.2 g, and C, 2g (P<0.05). These findings suggest that resistant duodenal ulcers are more responsive to cytoprotective agents than to antisecretory compounds.
