GASTRIC ANTI-SECRETORY, MUCOSAL PROTECTIVE, ANTI-PEPSIN AND ANTI-HELICOBACTER PROPERTIES OF RANITIDINE BISMUTH CITRATE

Ranitidine bismuth citrate is a novel compound formed from ranitidine and a bismuth citrate complex. In conscious dogs, ranitidine bismuth c itrate had similar activity to ranitidine hydrochloride as an inhibito r of histamine-induced gastric acid secretion when oral doses containi ng equivalent amounts of ranitidine base (0.1 or 0.3 mg/kg) were compa red. In the rat, ranitidine bismuth citrate (3-30 mg/kg p.o.) prevente d gastric mucosal damage induced by ethanol (fundic damage) and indome thacin (antral damage). Ranitidine hydrochloride and tripotassium dici trato bismuthate were also effective against indomethacin-induced dama ge, but were both significantly less potent than ranitidine bismuth ci trate in this model. Ranitidine hydrochloride was inactive against eth anol-induced damage. In vitro, ranitidine bismuth citrate (I mmol/L) i nhibited human pepsin isoenzymes 1, 2, 3 and 5. Pepsin 1 was inhibited to a similar extent by ranitidine bismuth citrate. bismuth citrate an d tripotassium dicitrato bismuthate at concentrations equivalent to 1 mmol/L bismuth, but ranitidine (I mmol/L) was inactive. Ranitidine bis muth citrate was more potent than tripotassium dicitrato bismuthate as an inhibitor of pepsins 2, 3 and 5. Ranitidine bismuth citrate inhibi ted both Helicobacter pylori (effective concentration 4-32 mug bismuth /ml) and H. mustelae (1-4 mug bismuth/ml); similar results were obtain ed with tripotassium dicitrato bismuthate. Bismuth citrate was slightl y less effective, and ranitidine hydrochloride was inactive (> 125 mug /ml). In ferrets naturally colonized with H. mustelae, oral treatment with ranitidine bismuth citrate, 12 or 24 mg/kg twice daily for 4 week s, caused a dose related clearance of H. mustelae. Qualitatively simil ar results were obtained in a small study with tripotassium dicitrato bismuthate and bismuth citrate.