Tripotassium dicitrato bismuthate

Under the effect of gastric acid, a precipitate is formed from tripotassium dicitrato bismuthate, which adheres primarily to the ulcerated area and inhibits the activity of pepsin. Tripotassium dicitrato bismuthate also protects the mucosa by stimulating the synthesis and secretion of endogenous prostaglandins, hence increasing bicarbonate and mucin production. In addition, tripotassium dicitrato bismuthate has antibacterial activity against Helicobacter pylori. Eradication of this bacteria is followed by an improvement in the histological picture and symptomatic improvement.

Pharmacodynamic effects

Tripotassium dicitrato bismuthate contributes to the healing of a high percentage of gastric and duodenal ulcers. Its antibacterial effect is associated with a lower frequency of ulcer recurrence in the first year after treatment discontinuation compared to some other agents.

Absorption

Tripotassium dicitrato bismuthate exerts a local action. However, small amounts of bismuth are absorbed (less than 0.2% of the dose) during therapy.

Distribution

Bismuth is distributed mainly into the kidneys. Only trace amounts can be detected in other organs.

Biotransformation

Tripotassium dicitrato bismuthate precipitates locally in the stomach under the influence of gastric acid, forming insoluble compounds, possibly bismuth oxychloride and bismuth citrate.

Elimination

The vast majority of the ingested bismuth is excreted with faeces. Of the small amount that is absorbed, urinary clearance is approximately 50 mL/min. At least a 3-compartment model is needed to describe the excretion of bismuth over time. The half-life is 5-11 days.

Oral single-dose of bismuth did not increase mortalities in rats at doses up to 2000 mg/kg. There were no significant changes attributed to treatment with bismuth on clinical signs, body weights, food consumption, haematology, clinical chemistry, urinalysis, organ weights, necropsy, or histopathological findings in the 28-day repeated oral dose toxicity study. The no-observed-adverseeffect level (NOAEL) of bismuth was determined to be 1000 mg/kg for males and females. No signs of hepatotoxicity were observed. There was also no presence of histopathological changes in the bone marrow or the lymphatic organs (thymus, spleen, lymph nodes).

The mutagenicity of bismuth cannot be assessed due to many shortcomings of the studies.

No definitive studies on the effects of bismuth citrate administration on male or female fertility and early embryonic development have been conducted. In rabbits maternal toxicity was apparent. However, no adverse effects upon pre- or post-implantation loss, numbers of viable foetuses or foetal development were observed. Tripoteassium dicitratobismuthate was not considered phototoxic.