Bismuth subcitrate potassium

Identification

Name
Bismuth subcitrate potassium
Accession Number
DB09275  (DBSALT001961)
Type
Small Molecule
Groups
Approved, Investigational
Description

A bismuth compound used for peptic ulcer and gastro-oesophageal reflux disease (GORD).

Structure
Thumb
Synonyms
  • Bismuth subcitrate potassium anhydrous
Product Ingredients
IngredientUNIICASInChI Key
Bismuth subcitrate potassium monohydrateR3O80H60KXNot AvailableVBVVJMZCAZRTKA-UHFFFAOYSA-H
Active Moieties
NameKindUNIICASInChI Key
Bismuth cationionicZS9CD1I8YE23713-46-4JDIBGQFKXXXXPN-UHFFFAOYSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
PyleraBismuth subcitrate potassium monohydrate (40 mg) + Metronidazole (125 mg) + Tetracycline hydrochloride (125 mg)CapsuleOralAptalis Pharma Inc.Not applicableNot applicableCanada
PyleraBismuth subcitrate potassium monohydrate (140 mg/1) + Metronidazole (125 mg/1) + Tetracycline hydrochloride (125 mg/1)CapsuleOralAxcan Pharma US, Inc.2007-05-012011-06-14Us
PyleraBismuth subcitrate potassium monohydrate (140 mg/1) + Metronidazole (125 mg/1) + Tetracycline hydrochloride (125 mg/1)CapsuleOralPhysicians Total Care, Inc.2010-08-18Not applicableUs
PyleraBismuth subcitrate potassium monohydrate (140 mg/1) + Metronidazole (125 mg/1) + Tetracycline hydrochloride (125 mg/1)CapsuleOralAllergan, Inc.2013-08-01Not applicableUs
Categories
UNII
BQE6KE1T4H
CAS number
880149-29-1
Weight
Average: 780.654
Monoisotopic: 779.79034
Chemical Formula
C12H8BiK5O14
InChI Key
YDDTTXDPCSCLKY-UHFFFAOYSA-H
InChI
InChI=1S/2C6H7O7.Bi.5K/c2*7-3(8)1-6(13,5(11)12)2-4(9)10;;;;;;/h2*1-2H2,(H,7,8)(H,9,10)(H,11,12);;;;;;/q2*-1;+3;5*+1/p-6
IUPAC Name
bismuth(3+) pentapotassium bis(2-oxidopropane-1,2,3-tricarboxylate)
SMILES
[K+].[K+].[K+].[K+].[K+].[Bi+3].[O-]C(=O)CC([O-])(CC([O-])=O)C([O-])=O.[O-]C(=O)CC([O-])(CC([O-])=O)C([O-])=O

Pharmacology

Indication

For the treatment of peptic ulcer and gastro-oesophageal reflux disease (GORD). Treatment of inflammatory and erosive-ulcerous diseases of gastric and duodenal mucosa: gastritis, ulcer disease of the stomach and duodenum, functional non-ulcerous dyspepsia, erosive duodenitis, post-operative inflammatory and erosive changes – anastomositis, peptic ulcer of anastomosis

Associated Conditions
Pharmacodynamics

Bismuth subcitrate is very effective in the treatment of gastroduodenal disorders and appears to act via several mechanisms. It has little acid-neutralizing effect and does not affect acid secretion.

Mechanism of action

Colloidal bismuth subcitrate is very effective in the treatment of gastroduodenal disorders and appears to act via several mechanisms. It has little acid-neutralizing effect and does not affect acid secretion. It is uncertain whether it affects pepsin secretion, but it does inhibit peptic activity. It causes an increase in mucus glycoprotein secretion and may also bind to the gastric mucus layer to act as a diffusion barrier to HCl. It accelerates ulcer healing and causes an accumulation of epidermal growth factor around the ulcer. In addition, it has a cytoprotective effect and increases mucosal secretion of prostaglandins and bicarbonate. It has bactericidal effects against Helicobacter pylori (which is associated with gastritis and peptic ulcers). It also prevents adhesion of H. pylori to epithelial cells and can inhibit enzymes secreted by H. pylori, such as proteases, lipases, glycosidases, and phospholipases.

TargetActionsOrganism
UATP-dependent Clp protease ATP-binding subunit ClpX
antagonist
Helicobacter pylori (strain ATCC 700392 / 26695)
Absorption

The mean peak whole-blood bismuth level after ingestion of colloidal bismuth subcitrate (214 mg bismuth) was more than 50 mg/liter and occurred at 30 minutes. After ingestion of bismuth subnitrate (205 mg bismuth), however, there was no evidence of bismuth absorption into blood, although in three of the volunteers who took bismuth subnitrate a week after colloidal bismuth subcitrate, baseline levels of blood bismuth were still elevated. Forty-five minutes after taking colloidal bismuth subcitrate, mean plasma levels for all five volunteers were also assessed and were 79.76 microg/liter as compared to blood levels of 47.6 microg/liter.

Volume of distribution
Not Available
Protein binding

>90%

Metabolism
Not Available
Route of elimination

Elimination of bismuth is primarily through urinary and biliary routes.

Half life

The elimination half-life of bismuth is approximately 5 days

Clearance

The rate of renal elimination appears to reach steady state 2 weeks after treatment discontinuation with similar rates of elimination at 6 weeks after discontinuation. The average urinary elimination of bismuth is 2.6% per day in the first two weeks after discontinuation (urine drug concentrations 24 to 250 mcg/mL) suggesting tissue accumulation and slow elimination.

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcepromazineAcepromazine may increase the neurotoxic activities of Bismuth subcitrate potassium.
AceprometazineAceprometazine may increase the neurotoxic activities of Bismuth subcitrate potassium.
AcetophenazineAcetophenazine may increase the neurotoxic activities of Bismuth subcitrate potassium.
AlimemazineAlimemazine may increase the neurotoxic activities of Bismuth subcitrate potassium.
AmineptineAmineptine may increase the neurotoxic activities of Bismuth subcitrate potassium.
AmisulprideAmisulpride may increase the neurotoxic activities of Bismuth subcitrate potassium.
AmitriptylineAmitriptyline may increase the neurotoxic activities of Bismuth subcitrate potassium.
AmitriptylinoxideBismuth subcitrate potassium may increase the neurotoxic activities of Amitriptylinoxide.
AmoxapineAmoxapine may increase the neurotoxic activities of Bismuth subcitrate potassium.
AmperozideAmperozide may increase the neurotoxic activities of Bismuth subcitrate potassium.
Food Interactions
Not Available

References

General References
  1. Lee SP: The mode of action of colloidal bismuth subcitrate. Scand J Gastroenterol Suppl. 1991;185:1-6. [PubMed:1957120]
  2. Wagstaff AJ, Benfield P, Monk JP: Colloidal bismuth subcitrate. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in peptic ulcer disease. Drugs. 1988 Aug;36(2):132-57. [PubMed:3053124]
  3. Phillips RH, Whitehead MW, Lacey S, Champion M, Thompson RP, Powell JJ: Solubility, absorption, and anti-Helicobacter pylori activity of bismuth subnitrate and colloidal bismuth subcitrate: In vitro data Do not predict In vivo efficacy. Helicobacter. 2000 Sep;5(3):176-82. [PubMed:10971684]
  4. FDA Label [Link]
External Links
PubChem Compound
118987133
PubChem Substance
347827831
ChemSpider
34989447
Wikipedia
Bismuth_subcitrate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentFatty Liver / Insulin Resistance / Liver Dysfunction1
3CompletedTreatmentHelicobacter Infections1
3RecruitingTreatmentDuodenal Ulcer1
3WithdrawnTreatmentBacterial Infection Due to Helicobacter Pylori (H. Pylori)1
4RecruitingTreatmentNSAID-induced Gastropathy1
4Unknown StatusTreatmentBacterial Infection Due to Helicobacter Pylori (H. Pylori)1
Not AvailableCompletedTreatmentBacterial Infection Due to Helicobacter Pylori (H. Pylori)1
Not AvailableRecruitingTreatmentBacterial Infection Due to Helicobacter Pylori (H. Pylori)3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6350468No2002-02-262018-12-14Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility13.8 mg/mLALOGPS
logP0.79ALOGPS
logP-1.3ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)3.05ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area143.45 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity78.69 m3·mol-1ChemAxon
Polarizability13.97 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
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as tricarboxylic acids and derivatives. These are carboxylic acids containing exactly three carboxyl groups.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Tricarboxylic acids and derivatives
Direct Parent
Tricarboxylic acids and derivatives
Alternative Parents
Carboxylic acid salts / Carboxylic acids / Organic potassium salts / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds / Alkoxides / Organic cations
Substituents
Tricarboxylic acid or derivatives / Carboxylic acid salt / Organic alkali metal salt / Carboxylic acid / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organic potassium salt / Organic salt / Alkoxide
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Helicobacter pylori (strain ATCC 700392 / 26695)
Pharmacological action
Unknown
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
ATP-dependent specificity component of the Clp protease. It directs the protease to specific substrates. Can perform chaperone functions in the absence of ClpP.
Gene Name
clpX
Uniprot ID
O25926
Uniprot Name
ATP-dependent Clp protease ATP-binding subunit ClpX
Molecular Weight
50352.815 Da
References
  1. Lee SP: The mode of action of colloidal bismuth subcitrate. Scand J Gastroenterol Suppl. 1991;185:1-6. [PubMed:1957120]

Drug created on October 28, 2015 16:23 / Updated on November 02, 2018 08:49