Bismuth subnitrate

Identification

Name
Bismuth subnitrate
Accession Number
DB13209
Type
Small Molecule
Groups
Approved
Description

Bismuth subnitrate, also referred to as bismuth oxynitrate or bismuthyl nitrate, is a highly water-soluble crystalline compound that has been used as a treatment for duodenal ulcers and anti-diarrheic agent [1]. The use of bismuth substrate as an active ingredient in over-the-counter antacids is approved by the FDA.

Structure
Thumb
Synonyms
  • Bismuth hydroxide nitrate oxide
  • Bismuth nitrate, basic
  • Bismuthum subnitricum
External IDs
C.I. 77169
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Hemorro-dol SupBismuth subnitrate (37.8 mg) + Balsam of Peru (22.6 mg) + Belladonna (11.25 mg) + Benzocaine (50 mg) + Bismuth subcarbonate (86.4 mg) + Boric acid (226.7 mg) + Ephedrine sulfate (2.5 mg) + Zinc oxide (226.7 mg)SuppositoryRectalProduits Francais Labs Inc.1981-12-311997-05-30Canada
Categories
UNII
H19J064BA5
CAS number
1304-85-4
Weight
Average: 1461.98
Monoisotopic: 1461.87284
Chemical Formula
Bi5H9N4O22
InChI Key
QGWDKKHSDXWPET-UHFFFAOYSA-E
InChI
InChI=1S/5Bi.4NO3.9H2O.O/c;;;;;4*2-1(3)4;;;;;;;;;;/h;;;;;;;;;9*1H2;/q5*+3;4*-1;;;;;;;;;;-2/p-9
IUPAC Name
pentabismuth(3+) ion nonahydroxide tetranitrate oxidandiide
SMILES
[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[O--].[Bi+3].[Bi+3].[Bi+3].[Bi+3].[Bi+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O

Pharmacology

Indication

Indicated for over-the-counter use as an antacid.

Pharmacodynamics

Bismuth subnitrate acts as an antacid that exert protective effects on the gastric mucosa [1]. In a double-blind endoscopically controlled study, bismuth substrate was demonstrated to be effective for symptomatic relief in duodenal ulcers [2]. In the alcohol model of mucosal injury in the rat, bismuth substrate was shown to be cytoprotective [2]. In a randomized clinical study consisting of patients with H. pylori-associated duodenal ulcer, adjunctive use of colloidal bismuth subnitrate in a short treatment regimen with omeprazole and clarithromycin resulted in improved eradication rate of H. pylori [3].

Mechanism of action

Based on the findings of a clinical investigation in patients with duodenal ulcer disease and healthy volunteers receiving oral bismuth subnitrate tablets, the protective effects of bismuth subnitrate may be secondary to endogenous mucosal prostaglandin (PGE2) production, which is one of the deficient factors observed in peptic ulcer disease [2]. Antacid neutralizing activity of bismuth subnitrate was demonstrated to have a significant postprandial effect on gastric pH [2].

Absorption

Bismuth subnitrate may undergo minimal gastrointestinal absorption which may be potentiated with concomitant administration of sulfhydryl compounds [5] when dissolved in citrate buffer solution [1]. Approximately 0.2% of orally administered bismuth is absorbed systematically from the gastrointestinal tract with the peak plasma concentration typically occurring within 1 hour [5].

Volume of distribution

Bismuth has been shown to accumulate preferentially in the kidneys [1].

Protein binding

Upon accumulation in the kidneys, bismuth may bind to a bismuth-metal binding protein in the kidney [4].

Metabolism

No pharmacokinetic data available.

Route of elimination

Bismuth may undergo both urinary and faecal excretion, however the exact proportion contributed by each route is still unknown [4].

Half life

The distribution half-life of bismuth is approximately 1 to 4 hours, and the elimination half-life is 5 to 11 days [5].

Clearance

No pharmacokinetic data available.

Toxicity

Reported oral dose range for moderate toxicity or possibly lethal toxicity in humans is 0.5-5 g/kg [5]. Nephropathy, encephalopathy, osteoarthropathy, gingivitis, stomatitis and colitis have been attributed to bismuth toxicity in humans [4].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
16-BromoepiandrosteroneThe bioavailability of 16-Bromoepiandrosterone can be decreased when combined with Bismuth subnitrate.
19-norandrostenedioneThe bioavailability of 19-norandrostenedione can be decreased when combined with Bismuth subnitrate.
2,5-Dimethoxy-4-ethylamphetamineBismuth subnitrate may decrease the excretion rate of 2,5-Dimethoxy-4-ethylamphetamine which could result in a higher serum level.
2,5-Dimethoxy-4-ethylthioamphetamineBismuth subnitrate may decrease the excretion rate of 2,5-Dimethoxy-4-ethylthioamphetamine which could result in a higher serum level.
3,4-MethylenedioxyamphetamineBismuth subnitrate may decrease the excretion rate of 3,4-Methylenedioxyamphetamine which could result in a higher serum level.
4-Bromo-2,5-dimethoxyamphetamineBismuth subnitrate may decrease the excretion rate of 4-Bromo-2,5-dimethoxyamphetamine which could result in a higher serum level.
5-androstenedioneThe bioavailability of 5-androstenedione can be decreased when combined with Bismuth subnitrate.
AcepromazineBismuth subnitrate can cause a decrease in the absorption of Acepromazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
AceprometazineBismuth subnitrate can cause a decrease in the absorption of Aceprometazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
AcetaminophenBismuth subnitrate can cause a decrease in the absorption of Acetaminophen resulting in a reduced serum concentration and potentially a decrease in efficacy.
Food Interactions
Not Available

References

General References
  1. Kondo Y, Himeno S, Satoh M, Naganuma A, Nishimura T, Imura N: Citrate enhances the protective effect of orally administered bismuth subnitrate against the nephrotoxicity of cis-diamminedichloroplatinum. Cancer Chemother Pharmacol. 2004 Jan;53(1):33-8. doi: 10.1007/s00280-003-0706-9. Epub 2003 Oct 7. [PubMed:14530870]
  2. Pugh S, Lewin MR: Mechanism of action of Roter (bismuth subnitrate) in patients with duodenal ulcer disease and healthy volunteers. J Gastroenterol Hepatol. 1990 Jul-Aug;5(4):382-6. [PubMed:2129809]
  3. Forne M, Viver JM, Espinos JC, Coll I, Tresserra F, Garau J: Impact of colloidal bismuth subnitrate in the eradication rates of Helicobacter pylori infection-associated duodenal ulcer using a short treatment regimen with omeprazole and clarithromycin: a randomized study. Am J Gastroenterol. 1995 May;90(5):718-21. [PubMed:7733075]
  4. Slikkerveer A, de Wolff FA: Pharmacokinetics and toxicity of bismuth compounds. Med Toxicol Adverse Drug Exp. 1989 Sep-Oct;4(5):303-23. [PubMed:2682129]
  5. BISMUTH SUBNITRATE - National Library of Medicine HSDB Database - Toxnet [Link]
External Links
KEGG Drug
D01642
KEGG Compound
C13102
ChemSpider
32699716
ChEBI
31293
Wikipedia
Bismuth_oxynitrate
ATC Codes
A02BX12 — Bismuth subnitrate

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SuppositoryRectal
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)Decomposes at 260MSDS
boiling point (°C)Decomposes at 260MSDS
water solubilityInsolubleMSDS
Predicted Properties
PropertyValueSource
logP0.84ChemAxon
pKa (Strongest Basic)-9.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area66.2 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity8.35 m3·mol-1ChemAxon
Polarizability3.28 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of inorganic compounds known as post-transition metal nitrates. These are inorganic compounds in which the largest oxoanion is nitrate, and in which the heaviest atom not in an oxoanion is a post-transition metal.
Kingdom
Inorganic compounds
Super Class
Mixed metal/non-metal compounds
Class
Post-transition metal oxoanionic compounds
Sub Class
Post-transition metal nitrates
Direct Parent
Post-transition metal nitrates
Alternative Parents
Post-transition metal salts / Inorganic salts / Inorganic oxides / Inorganic hydrides
Substituents
Post-transition metal nitrate / Inorganic post-transition metal salt / Inorganic hydride / Inorganic oxide / Inorganic salt
Molecular Framework
Not Available
External Descriptors
Not Available

Drug created on June 23, 2017 14:37 / Updated on August 02, 2018 06:49