General Comments

The only significant human exposure to bismuth involves pharmaceutical uses. A number of trivalent and, rarely, pentavalent salts of bismuth have been used orally or intramuscularly over the past two centuries for the treatment of a number of conditions: syphilis, malaria, hypertension, warts, stomatitis, upper respiratory tract infections, amebiasis, dyspepsia and diarrhea. Bismuth compounds have also been used as radiocontrast agents in diagnostic testing and as topical astringents having slight antiseptic action (1). With the introduction of more effective therapeutic agents, primarily antibiotics and antimicrobials, the internal use of certain trivalent bismuth salts (subnitrates, subcarbonates, subgallates, tartrates, subcitrates, and subsalicylates) is now limited primarily to oral preparations for the prevention and treatment of gastric and intestinal disorders, such as ulcers and diarrhea. Available as over-the-counter products, the (presumed) insoluble bismuth salts were long considered safe, being poorly absorbed from the GI tract. Recently, however, long-term, unmonitored, and indiscriminate use of certain Bi salts, particularly lipid-soluble subgallates and subnitrates, has been associated with a number of toxic effects in humans, primarily (reversible) encephalopathy and nephropathy (2). At present, use of colloidal bismuth subcitrate (CBS; |

De-Nol) and bismuth subsalicylate (BSS; Pepto-Bismol) is considered safe and f effective for the treatment of diarrhea; both salts have antimicrobial activity against causative pathogens. More controversial (3) are the claims of their thera- ^

peutic activity on both gastric and duodenal ulcers, based on the combination of bismuth's specific activity against the etiologic agent (Helicobacter pylori) and J

the formation of a protective coating by colloidal bismuth compounds in the ulcer crater, thus providing a diffusion barrier to HCl and pepsin (4,5). Low- |

level absorption of bismuth, resulting in nontoxic blood levels (below 50 |g/L), |

was noted upon oral administration of tripotassium dicitratobismuthate to both healthy volunteers and patients with gastroduodenal ulcers (6). |

Upon absorption, bismuth equilibrates between bone, soft tissues, and <->

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