title: Gastric anti-secretory, mucosal protective, anti-pepsin and anti-Helicobacter properties of ranitidine bismuth citrate.
abstract: 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.
authors.affiliation: Glaxo Group Research Ltd, Ware, Herts, UK.
authors.forename: R
authors.initials: R
authors.lastname: Stables
authors.forename: C J
authors.initials: CJ
authors.lastname: Campbell
authors.forename: N M
authors.initials: NM
authors.lastname: Clayton
authors.forename: J W
authors.initials: JW
authors.lastname: Clitherow
authors.forename: C J
authors.initials: CJ
authors.lastname: Grinham
authors.forename: A A
authors.initials: AA
authors.lastname: McColm
authors.forename: A
authors.initials: A
authors.lastname: McLaren
authors.forename: M A
authors.initials: MA
authors.lastname: Trevethick
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001729:Bismuth / Q000494:pharmacology* / Q000627:therapeutic use; D002951:Citrates / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D000431:Ethanol; D005260:Female; D005289:Ferrets; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D016481:Helicobacter Infections / Q000382:microbiology / Q000517:prevention & control*; D016480:Helicobacter pylori; D006801:Humans; D007213:Indomethacin; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D008826:Microbial Sensitivity Tests; D009942:Organometallic Compounds / Q000494:pharmacology; D010434:Pepsin A / Q000037:antagonists & inhibitors*; D011899:Ranitidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000897:Anti-Ulcer Agents; D002951:Citrates; D007527:Isoenzymes; D009942:Organometallic Compounds; D000431:Ethanol; C073340:ranitidine bismuth citrate; D011899:Ranitidine; D010434:Pepsin A; C002791:bismuth tripotassium dicitrate; D001729:Bismuth; D007213:Indomethacin