Gastric anti-secretory, mucosal protective, anti-pepsin and anti-Helicobacter properties of ranitidine bismuth citrate

Aliment Pharmacol Ther. 1993 Jun;7(3):237-46. doi: 10.1111/j.1365-2036.1993.tb00094.x.


Ranitidine bismuth citrate is a novel compound formed from ranitidine and a bismuth citrate complex. In conscious dogs, ranitidine bismuth citrate had similar activity to ranitidine hydrochloride as an inhibitor of histamine-induced gastric acid secretion when oral doses containing equivalent amounts of ranitidine base (0.1 or 0.3 mg/kg) were compared. In the rat, ranitidine bismuth citrate (3-30 mg/kg p.o.) prevented gastric mucosal damage induced by ethanol (fundic damage) and indomethacin (antral damage). Ranitidine hydrochloride and tripotassium dicitrato bismuthate were also effective against indomethacin-induced damage, but were both significantly less potent than ranitidine bismuth citrate in this model. Ranitidine hydrochloride was inactive against ethanol-induced damage. In vitro, ranitidine bismuth citrate (1 mmol/L) inhibited human pepsin isoenzymes 1, 2, 3 and 5. Pepsin 1 was inhibited to a similar extent by ranitidine bismuth citrate, bismuth citrate and tripotassium dicitrato bismuthate at concentrations equivalent to 1 mmol/L bismuth, but ranitidine (1 mmol/L) was inactive. Ranitidine bismuth citrate was more potent than tripotassium dicitrato bismuthate as an inhibitor of pepsins 2, 3 and 5. Ranitidine bismuth citrate inhibited both Helicobacter pylori (effective concentration 4-32 micrograms bismuth/ml) and H. mustelae (1-4 micrograms bismuth/ml); similar results were obtained with tripotassium dicitrato bismuthate. Bismuth citrate was slightly less effective, and ranitidine hydrochloride was inactive (> 125 micrograms/ml). In ferrets naturally colonized with H. mustelae, oral treatment with ranitidine bismuth citrate, 12 or 24 mg/kg twice daily for 4 weeks, caused a dose related clearance of H. mustelae. Qualitatively similar results were obtained in a small study with tripotassium dicitrato bismuthate and bismuth citrate.

MeSH terms

  • Animals
  • Anti-Ulcer Agents / pharmacology*
  • Anti-Ulcer Agents / therapeutic use
  • Bismuth / pharmacology*
  • Bismuth / therapeutic use
  • Citrates / pharmacology*
  • Citrates / therapeutic use
  • Dogs
  • Ethanol
  • Female
  • Ferrets
  • Gastric Acid / metabolism*
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / pathology
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / prevention & control*
  • Helicobacter pylori*
  • Humans
  • Indomethacin
  • Isoenzymes / antagonists & inhibitors
  • Male
  • Microbial Sensitivity Tests
  • Organometallic Compounds / pharmacology
  • Pepsin A / antagonists & inhibitors*
  • Ranitidine / analogs & derivatives*
  • Ranitidine / pharmacology
  • Ranitidine / therapeutic use
  • Rats
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / prevention & control*


  • Anti-Ulcer Agents
  • Citrates
  • Isoenzymes
  • Organometallic Compounds
  • Ethanol
  • ranitidine bismuth citrate
  • Ranitidine
  • Pepsin A
  • bismuth tripotassium dicitrate
  • Bismuth
  • Indomethacin