Colloidal bismuth subcitrate. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in peptic ulcer disease.

Abstract

Colloidal bismuth subcitrate (CBS) possesses at least equal efficacy with histamine H2-receptor antagonist drugs in the treatment of peptic ulcer disease. However, CBS has the advantage of slower ulcer relapse rates than those seen after initial healing with the H2-antagonists. It has been postulated that this effect may be partly due to the antibacterial properties of CBS against Campylobacter pylori, a bacterium found in the gastric mucosa and gastric metaplasia within the duodenum of most patients with peptic ulcer and closely associated with gastritis. However, the role of C. pylori in the aetiology of peptic disease is far from clear. The mechanism by which CBS heals ulcers has not been fully elucidated, but several actions may be involved. CBS and mucus form a glycoprotein-bismuth complex in vitro. This provides a diffusion barrier to HCl and may, therefore, provide a protective coating in the ulcer crater which allows healing of the lesion to occur. Prostaglandin E2 production is also stimulated by CBS with subsequent secretion of alkali into the mucus layer. In addition, CBS has a direct inhibitory effect on C. pylori. Administration of CBS results in low levels of bismuth absorption. Most of the ingested bismuth is excreted as bismuth sulphide, causing blackening of the faeces, and the small amount absorbed is excreted in the urine. Bismuth intoxication (encephalopathy) has been reported with prolonged administration of bismuth salts, and there has been 1 report of similar intoxication in a patient receiving unusually high doses of CBS for a prolonged period. However, no such intoxication has been reported with CBS used at its recommended dosage in the acute treatment of peptic ulcer disease, and no other serious adverse effects have been associated with CBS. Tissue accumulation during prolonged therapy seems likely, and the safety of CBS during long term maintenance therapy has not been established. The lack of effect on gastric acid secretion is seen as an added advantage for CBS, since prolonged drug-induced hypochlorhydria has been postulated to have potentially detrimental effects. Thus, while the role of C. pylori in peptic ulceration requires further clarification, CBS would appear to have an important place in the treatment of peptic ulcer disease with the advantage of relatively slow relapse rates after initial healing and treatment discontinuation.