What is bismuth subcitrate?

Bismuth Subcitrate: Properties and Clinical Applications

Bismuth subcitrate is a bismuth salt primarily used in combination therapy for Helicobacter pylori eradication, serving as a key component in bismuth quadruple therapy regimens due to its antimicrobial properties and ability to overcome antibiotic resistance. 1, 2

Chemical Composition and Properties

• Bismuth subcitrate potassium is a white to off-white powder that is soluble in water and functions as a double salt of bismuth citrate and potassium citrate, containing an additional part of potassium hydroxide 3
• The schematized empirical molecular formula of bismuth subcitrate potassium is BiK5(OH)2(C6H5O7)2·H2O, with an equivalent theoretical molecular formula of BiC12H14K5O17 and a molecular mass of 834.7 3
• When used in pharmaceutical preparations, bismuth subcitrate is typically formulated at a dosage of 120-140 mg per tablet or capsule 2

Therapeutic Applications

Role in H. pylori Eradication

• Bismuth subcitrate is a critical component of bismuth quadruple therapy, which is recommended as first-line treatment for H. pylori eradication in areas with high clarithromycin resistance (>15-20%) 2, 4
• The standard bismuth quadruple therapy regimen includes bismuth subcitrate (120-140 mg) 3-4 times daily, tetracycline hydrochloride (500 mg) 4 times daily, metronidazole (500 mg) 3-4 times daily, and a proton pump inhibitor twice daily 2
• Bismuth-containing quadruple therapy achieves eradication rates >80%, even in the presence of antibiotic resistance 4

Mechanism of Action

• Bismuth subcitrate has multiple mechanisms of action against H. pylori:
  • Direct bactericidal effects against H. pylori 5
  • Prevention of H. pylori adhesion to epithelial cells 5
  • Inhibition of enzymes secreted by H. pylori, including proteases, lipases, glycosidases, and phospholipases 5
  • Forms a protective coating on the gastric mucosa, acting as a diffusion barrier to hydrochloric acid 5

Additional Therapeutic Effects

• Increases mucus glycoprotein secretion and enhances the gastric mucosal barrier 5
• Demonstrates cytoprotective effects and increases mucosal secretion of prostaglandins and bicarbonate 5
• Accelerates ulcer healing and causes accumulation of epidermal growth factor around ulcers 5
• Effective in treating non-ulcer dyspepsia, with studies showing symptom improvement in up to 82% of patients 6, 7

Clinical Use Guidelines

Recommended Regimens

• The American Gastroenterological Association recommends bismuth subcitrate as part of quadruple therapy with metronidazole, tetracycline, and a PPI for H. pylori eradication 2
• The optimal duration of treatment is 14 days, especially in areas with high metronidazole resistance, though 10-day regimens may be acceptable if proven locally effective 1, 2
• In patients with penicillin allergy in areas of high clarithromycin resistance, bismuth-containing quadruple therapy is the preferred treatment option 4

Absorption and Pharmacokinetics

• Orally absorbed bismuth is distributed throughout the body and is highly bound to plasma proteins (>90%) 3
• The elimination half-life of bismuth is approximately 5 days in both blood and urine 3
• Elimination occurs primarily through urinary and biliary routes, with an average urinary elimination rate of 2.6% per day in the first two weeks after discontinuation 3

Safety Considerations

• Treatment periods with bismuth-containing compounds should not exceed 6-8 weeks, followed by 8-week bismuth-free intervals, due to potential tissue accumulation 8
• Bismuth absorption is minimal (approximately 0.2% of the ingested dose), but sequestration can occur in multiple tissue sites even with conventional dosing over a 6-week period 8
• Symptoms of bismuth subcitrate potassium overdosage are not well documented 3
• The efficacy of bismuth in H. pylori eradication is not related to its absorption, suggesting that poorly absorbed bismuth preparations can be effective while minimizing systemic exposure 9

Follow-up After Treatment

• Success of H. pylori eradication should be confirmed at least 4 weeks after completing treatment 4
• The urea breath test (UBT) or a validated monoclonal stool test are recommended for confirming eradication 1, 4
• Prior to testing, antibiotics and bismuth should be withheld for at least 4 weeks, and PPIs should be withheld for at least 7 days 1