Prussian blue

Identification

Summary

Prussian blue is a chelating agent used to reduce the extent of systemic contamination with radioactive cesium and/or radioactive or non-radioactive thallium.

Brand Names
Radiogardase
Generic Name
Prussian blue
DrugBank Accession Number
DB06783
Background

Prussian blue is described as a deep blue pigment that is produced when the oxidation of ferrous ferrocyanide salts occurs. It contains ferric hexacyanoferrate(II) in a cubic lattice crystal structure. It is insoluble in water but also tends to form a colloid thus can exist in either colloidal or water-soluble form, and an insoluble form. It is orally administered for clinical purposes to be used as an antidote for certain kinds of heavy metal poisoning, such as thallium and radioactive isotopes of caesium. Prussian blue is included in the World Health Organization Model List of Essential Medicines as a specific antidote used in poisonings to provide symptomatic and supportive treatment. It was also administered in individuals exposed to 137-Cs+ during Goiânia accident, one of the worst radioactive contamination incidents that occured in Brazil, 1983.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 859.239
Monoisotopic: 859.599884
Chemical Formula
C18Fe7N18
Synonyms
  • Berlin blue
  • Ferric ferrocyanide
  • Ferric hexacyanoferrate
  • Ferric hexacyanoferrate(II)
  • Ferrocin
  • Iron(III) ferrocyanide
  • Iron(III) hexacyanoferrate(II)
  • Paris blue
  • Parisian blue
  • Prussian blue insoluble

Pharmacology

Indication

Indicated for treatment of patients with known or suspected internal contamination with radioactive cesium and/or radioactive or non-radioactive thallium to increase their rates of elimination.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Prussian blue is an insoluble radioactive metals chelating agent and absorbent. It acts by ion-exchange, adsorption, and mechanical trapping within the crystal structure and has a very high affinity for radioactive and non-radioactive cesium and thallium. The antidote therapy greatly minimizes the extent of contamination and reduces the half life of radioactive isotopes which have relatively long physicall half life and uniform tissue distribution. Data suggest that in humans, Prussian blue can reduce cesium’s half-life by approximately 43% and reduce total body burdens by significantly increasing the feces-to-urine excretion ratio 4.

Mechanism of action

Prussian blue binds cesium and thallium isotopes in the gastrointestinal tract after ingestion or excreted in the bile by the liver, therby reduces gastrointestinal reabsorption into the enterohepatic circulation. It serves as an ion exchanger for univalent cations and it preferentially binds to cesium or thallium as its affinity for cations increases as the ionic radius of the cation increases 1. Prussian blue exchanges potassium for cesium or thallium at the surface of the crystal in the intestinal lumen. The insoluble complex is excreted without being absorbed from the intestinal walls. Insoluble prussian blue decreases the half life of cesium by 33% and from 3.8 to 2.2 days for thallium 3. The rate of cesium and thallium elimination is proportional to the dose and duration of prussian blue.

Absorption

It is poorly or not absorbed from the gastrointestinal tract walls after oral ingestion. Systemic absorption is assumed to be insignificant, with minimal release of cyanide from the complex. A small amount (approximately 2%) of the hexacyanoferrate ion was absorbed after oral ingestion of prussian blue but with no signs of decomposition. Prussian blue is not systemically bioavailable 9.

Volume of distribution

Histopathological examination of different organs showed no deposits of prussian blue after oral administration of insoluble prussian blue 9.

Protein binding

Not Available

Metabolism

No evidence of decomposition after oral ingestion 7. Prussian blue does not undergo hepatic metabolism; use of the drug is not contraindicated in patients with hepatic impairment 9.

Route of elimination

It predominantly depends on fecal excretion, and does not depend on renal elimination. Based on animal data, 99% of a single dose of 40 mg of labeled insoluble Prussian blue was excreted unchanged in feces 9.

Half-life

Not Available

Clearance

The clearance from the body depends on the gastrointestinal tract transit time 9.

Adverse Effects
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Toxicity

Mild cases of hypokalemia have been reported as prussian blue may bind other electrolytes found in the gastrointestinal tract. Gastrointestinal symptoms include abdominal pain or distension. Constipation may occur resulting in further decreased gastrointestinal motility and increased reabsorption and exposure time to radioisotopes, but may may be treated with a fiber based laxative and/or a high fiber diet. Oral dose that results in acute toxicity in mouse, rat and rabbit is >8000mg/kg. Based on reported adverse events and mechanism of action, possible overdose symptoms may include obstipation, obstruction, or severe decrease in electrolytes.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Alendronic acidPrussian blue can cause a decrease in the absorption of Alendronic acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
AlmasilateAlmasilate can cause a decrease in the absorption of Prussian blue resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium phosphateAluminium phosphate can cause a decrease in the absorption of Prussian blue resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminum hydroxideAluminum hydroxide can cause a decrease in the absorption of Prussian blue resulting in a reduced serum concentration and potentially a decrease in efficacy.
AsenapineAsenapine can cause a decrease in the absorption of Prussian blue resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium carbonateCalcium carbonate can cause a decrease in the absorption of Prussian blue resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium PhosphatePrussian blue can cause a decrease in the absorption of Calcium Phosphate resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium phosphate dihydratePrussian blue can cause a decrease in the absorption of Calcium phosphate dihydrate resulting in a reduced serum concentration and potentially a decrease in efficacy.
CarbidopaPrussian blue can cause a decrease in the absorption of Carbidopa resulting in a reduced serum concentration and potentially a decrease in efficacy.
CefdinirPrussian blue can cause a decrease in the absorption of Cefdinir resulting in a reduced serum concentration and potentially a decrease in efficacy.
Interactions
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Food Interactions
No interactions found.

Products

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Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RadiogardaseCapsule500 mg/1OralHeyl Chem.-pharm. Fabrik GmbH & Co. KG2010-03-24Not applicableUS flag58060 0002 01 nlmimage10 8d3546fa

Categories

ATC Codes
V03AB31 — Prussian blue
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as organic transition metal salts. These are organic salt compounds containing a transition metal atom in its ionic form.
Kingdom
Organic compounds
Super Class
Organic salts
Class
Organic metal salts
Sub Class
Organic transition metal salts
Direct Parent
Organic transition metal salts
Alternative Parents
Organopnictogen compounds / Organonitrogen compounds / Hydrocarbon derivatives
Substituents
Aliphatic acyclic compound / Hydrocarbon derivative / Organic nitrogen compound / Organic transition metal salt / Organonitrogen compound / Organopnictogen compound
Molecular Framework
Not Available
External Descriptors
hexacyanoferrate(4-) salt (CHEBI:30069)
Affected organisms
Not Available

Chemical Identifiers

UNII
TLE294X33A
CAS number
14038-43-8
InChI Key
DNMNDNSFJMUUFM-UHFFFAOYSA-N
InChI
InChI=1S/18CN.7Fe/c18*1-2;;;;;;;/q;;;;;;;;;;;;;;;;;;3*-4;4*+3
IUPAC Name
tetrairon(3+) ion tris(hexacyanoirontetrauide)
SMILES
[Fe+3].[Fe+3].[Fe+3].[Fe+3].N#C[Fe-4](C#N)(C#N)(C#N)(C#N)C#N.N#C[Fe-4](C#N)(C#N)(C#N)(C#N)C#N.N#C[Fe-4](C#N)(C#N)(C#N)(C#N)C#N

References

General References
  1. Hoffman RS: Thallium toxicity and the role of Prussian blue in therapy. Toxicol Rev. 2003;22(1):29-40. [Article]
  2. Meggs WJ, Cahill-Morasco R, Shih RD, Goldfrank LR, Hoffman RS: Effects of Prussian blue and N-acetylcysteine on thallium toxicity in mice. J Toxicol Clin Toxicol. 1997;35(2):163-6. [Article]
  3. Thompson DF, Callen ED: Soluble or insoluble prussian blue for radiocesium and thallium poisoning? Ann Pharmacother. 2004 Sep;38(9):1509-14. Epub 2004 Jul 13. [Article]
  4. Thompson DF, Church CO: Prussian blue for treatment of radiocesium poisoning. Pharmacotherapy. 2001 Nov;21(11):1364-7. [Article]
  5. Dresow B, Nielsen P, Fischer R, Pfau AA, Heinrich HH: In vivo binding of radiocesium by two forms of Prussian blue and by ammonium iron hexacyanoferrate (II). J Toxicol Clin Toxicol. 1993;31(4):563-9. [Article]
  6. Jang SC, Hong SB, Yang HM, Lee KW, Moon JK, Seo BK, Huh YS, Roh C: Removal of Radioactive Cesium Using Prussian Blue Magnetic Nanoparticles. Nanomaterials (Basel). 2014 Nov 28;4(4):894-901. doi: 10.3390/nano4040894. [Article]
  7. Pearce J: Studies of any toxicological effects of Prussian blue compounds in mammals--a review. Food Chem Toxicol. 1994 Jun;32(6):577-82. [Article]
  8. World Health Organization Model List of Essential Medicines (19th List) [Link]
  9. FERRIC HEXACYANOFERRATE Toxnet [Link]
PubChem Compound
2724251
PubChem Substance
310264883
ChemSpider
20074656
RxNav
24902
ChEBI
30069
Wikipedia
Prussian_blue
FDA label
Download (208 KB)
MSDS
Download (77.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral500 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityMostly insoluble in hot or cold water. 6 mg/mL at 25 deg CMSDS
Predicted Properties
PropertyValueSource
logP-0.26ChemAxon
Physiological Charge-4ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area142.74 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity39.93 m3·mol-1ChemAxon
Polarizability16.92 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

Drug created on September 14, 2010 16:21 / Updated on June 12, 2020 16:52