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| Routes of administration | Oral |
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| ECHA InfoCard | 100.055.320 |
| Chemical and physical data | |
| Formula | C12H8BiK5O14 |
| Molar mass | 780.654 g·mol−1 |
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Bismuth subcitrate potassium is abismuth salt used in combination with antibiotics and aproton pump inhibitor for the treatment ofHelicobacter pylori infections.[1][2]
A fixed-dose combination with the antibioticsmetronidazole andtetracycline is sold under the trade namePylera.[3]
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A known side effect of bismuth salts is harmless and reversible darkening of tongue and stool by formation of bismuthsulfite.[3] Other side effects of bismuth containing combination therapies are often difficult to assign to a specific component.[citation needed]
Bismuth absorption is increased byranitidine andomeprazole.[3]
The mechanism of action of bismuth is not fully known. It has been reasoned to interfere with the function of the bacterialcell membrane,protein andcell wall synthesis, the enzymeurease,cell adhesion,ATP synthesis, and iron transport mechanisms.[3] Bismuth displaces nickel (Ni2+) from active sites of the bacterialurease (UreG), and other bacterialmetalloenzymes (e.g.,catalase,lipase,fumarase), thereby disrupting acid-neutralization capacity and energy metabolism of H. pylori.[4] Another possible mechanism of action is that the inhibition of bacterial enzyme result in bacterial growth arrest.[4] Bismuth particles inducevacuolization, cell wall degradation, membrane disintegration, and loss of adherence toepithelial cells of the host:[4] bismuth impairs bacterial adhesion to the gastric epithelium andbiofilm formation.[4]
Upon oral administration, bismuth subcitrate undergoes partial dissolution in the acidic gastric environment, with the majority of the dose localizing in the stomach.[5][4] Although the most of the dose remains unabsorbed,[6] a small portion enters into systemic circulation, and serum concentration reaches (Cmax at20–30 min)16–80 ng/mL - levels that exceed the minimum inhibitory concentration for H. pylori (1–8 μg/mL).[7][4][5] Co-administration withproton pump inhibitors (PPI) such asomeprazole or H2-antagonists such asfamotidine increases serum and tissue concentrations of bismuth, possibly due to greater solubility and less rapid precipitation in less acidic gastric juice.[5]
In the small intestine, unlike the stomach, bismuth subcitrate does not form stable binding layers or antimicrobial reservoirs. At the more alkaline pH, colloidal particles aggregate and precipitate without significant further dissolution or interaction with epithelial or microbial targets. There is no conclusive evidence for microbiological impact of bismuth in thesmall intestine when administered at therapeutic doses.[8] Upon entry into thelarge intestine (colon), bismuth is exposed to an anaerobic, sulfur-rich environment maintained by the gut microbiota. Here, it undergoes microbialmethylation and sulfidecomplexation, yielding species such as trimethylbismuth (TMBi) and insolublebismuth sulfide (Bi2S3), which is responsible for the black coloration of stool during therapy.[8] Despite high total bismuth concentrations in the colon, antimicrobial activity in the colon is negligible because dominant forms of bismuth recovered (insoluble bismuth sulfide and methylated derivatives like TMBi) are microbiologically inactive; transformation into bismuth sulfide not only curtails further absorption but also minimizes potential toxicity and flora disruption.[8]
Bismuth subcitrate potassium is a salt ofbismuth (Bi3+),potassium (K+) andcitrate (C6H4O4−7) in amolar ratio of about 1:5:2, with 3 moles of water. It contains about 25.6% (mass percent) bismuth, which is the activemoiety, and 22.9% potassium.[3][9] Other sources give somewhat different ratios of the constituents.
Outside of H. pylori eradication and ulcer management, the broader antimicrobial potential and gastric‑protective roles of bismuth subcitrate are not well studied in clinical trials; this is a potential research direction.[10][11] Bismuth is also studied on potentialantiviral andantileishmanial applications.[10][11]