RANITIDINE BISMUTH CITRATE - A NOVEL ANTIULCER AGENT WITH DIFFERENT PHYSICOCHEMICAL CHARACTERISTICS AND IMPROVED BIOLOGICAL-ACTIVITY TO A BISMUTH CITRATE-RANITIDINE ADMIXTURE

Background: Ranitidine bismuth citrate (RBC) is a new chemical entity for the treatment of peptic ulcer disease. Results: RBC is freely solu ble in water (more than 600 mg/mL at pH 4.6), whereas an equimolar adm ixture of its component molecules, bismuth citrate and ranitidine, for med an almost totally insoluble suspension. Even at very low pH values (around 2.0), the solubility of bismuth in ranitidine bismuth citrate was at least two-fold better than in the admixture. Comparison of sev eral physico-chemical characteristics indicated that RBC possessed sig nificantly different melting point properties, X-ray powder diffractio n patterns, infra-red spectra and C-13-NMR solid-state spectra to the admixture. Ranitidine bismuth citrate inhibited human pepsin isoenzyme s 1, 2, 3 and 5 but the admixture was inactive. RBC showed approximate ly two-fold greater anti-Helicobacter pylori activity in vitro than th e admixture (geometric mean minimum inhibitory concentrations of 12.5 and 25.7 mg/L, respectively) and was more rapidly bactericidal. In a m ouse model of gastric H. pylori colonization, 200 mg/kg of bismuth, gi ven as RBC, eradicated the organism from all mice while only 10% of in fections were eradicated by equivalent levels of bismuth in admixture form. Conclusion: It is believed that the significantly greater solubi lity of RBC, especially at lower pH values, is highly relevant to its better antipepsin and anti-H. pylori action compared to the insoluble admixture of bismuth citrate and ranitidine.