Prevention of duodenal ulcers in the rat using a combination of ranitidine and sucralphate in subtherapeutic doses.

Abstract

SUMMARY This study investigated whether ulcer prevention would be greater with the combined use of an acid-inhibiting agent, ranitidine, given together with a mucosal-protective agent, sucralphate. Duodenal ulcers were induced in rats with the secretagogues pentagastrin and bethanechol. Subtherapeutic doses of ranitidine (5 mg/kg/6 hours) and sucralphate (50 mg/6 hour) yielded an ulcer index of 4-0 and 4 1 respectively, not significantly different from the control (untreated) ulcer index of 4-3. Therapeutic doses of ranitidine (20 mg/kg) and sucralphate (200 mg/animal) gave an ulcer index of 0.4 and 0O5 respectively. Subtherapeutic doses of ranitidine and sucralphate given in combination yielded an ulcer index of 0-7. Thus, subtherapeutic doses of ranitidine and sucralphate given in combination had a synergistic effect equal to therapeutic doses of each of these drugs given alone. The therapeutic implications of combined acid inhibiting drugs with mucosal protective drugs is discussed.The time honoured equation of ulcer disease acidpepsin aggression vs mucosal resistance remains the mainstay of the therapeutic approach to ulcer disease. H2 histamine receptor antagonists and the mucosa-protective, or cytoprotective agents have been shown to promote ulcer healing in man. They also prevent ulcer formation by a large variety of ulcer-inducing techniques in animals.'3 There have been few investigations whether ulcer prevention would be greater with the combined use of an acid-inhibiting agent with a mucosal-protective agent. The effect of ranitidine, a histamine H2 receptor antagonist and sucralphate, a mucosalprotective agent, were investigated alone to establish therapeutic and subtherapeutic levels in an ulcer model; the combination of these drugs at subtherapeutic levels was then studied in the same animal model. ,ug/kg/min, and bethanechol 12 jug/kg/min, for 24 hours through a needle inserted between the shoulder blades. The rats were allowed reasonable mobility in cages 25x5x5 cm. Five sets of experiments were done.