Identification

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Name
Iopodic acid
Accession Number
DB09333
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Description

Iopodic acid, also known by the name of ipodate, is classified as a cholecystographic agent formed by a weak organic acid that contains a tri-iodinated benzene ring with iodine at positions 2, 4 and 6.1 Due to its particular structure, it presents a high degree of lipid solubility and a radiopaque property. It was developed and filed to the FDA by the company BRACCO. This drug was approved on March 15, 1962 but it is nowadays discontinued from the FDA and Health Canada. On September 22, 1981, ipodate was submitted again by the company Schering AG but it is currently under an inactive status.7

Structure
Thumb
Synonyms
  • Ipodate
Product Ingredients
IngredientUNIICASInChI Key
Ipodate calcium50S7W5M9ZZ1151-11-7HVZGHKKROPCBDE-UHFFFAOYSA-L
Ipodate sodiumF316LLW9WW1221-56-3ZFHZUGUCWJVEQC-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Oragrafin Sodium 0.5gmCapsule500 mgOralBracco Imaging S.P.A.1969-12-311999-07-30Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Categories
UNII
F604ZKI910
CAS number
5587-89-3
Weight
Average: 597.961
Monoisotopic: 597.81111
Chemical Formula
C12H13I3N2O2
InChI Key
YQNFBOJPTAXAKV-UHFFFAOYSA-N
InChI
InChI=1S/C12H13I3N2O2/c1-17(2)6-16-12-9(14)5-8(13)7(11(12)15)3-4-10(18)19/h5-6H,3-4H2,1-2H3,(H,18,19)
IUPAC Name
3-(3-{[(dimethylamino)methylidene]amino}-2,4,6-triiodophenyl)propanoic acid
SMILES
CN(C)C=NC1=C(I)C=C(I)C(CCC(O)=O)=C1I

Pharmacology

Indication

Iopodic acid is available as a cholecystographic agent. This denomination indicates the iopodic acid is a radiopaque substance that can be used to visualize the gallbladder and biliary channels in abdominal X-ray.8,4 An abdominal X-ray uses a minimal amount of ionizing radiation to produce pictures of the inside of the abdominal cavity. It is commonly used to evaluate the stomach, liver, intestines, and spleen.9

Iopodic acid has also been indicated for the treatment of hyperthyroidism such as Graves disease.2,3 Hyperthyroidism refers to any condition where there is too much thyroid hormone produced in the body (overactive thyroid). When the overactivity involves the entire thyroid gland, it is known as Grave's disease.10

Pharmacodynamics

The thyroid effects of iopodic acid are related to the blocking of the more potent form of the thyroid hormone. It also blocks thyroid hormone release and it can interfere with its synthesis in some patients. The effects of iopopdic acid on some diseases, such as Graves disease, have been shown not to be as effective and to present a relapse after discontinuation.2,3 The effects of iopodic acid on thyroid has been proven to produce an inactivation of approximately 80% of the type II deiodinase in pituitary and cerebral cortex.4

Mechanism of action

For cholecystography, iopodic acid blocks the X-rays as they pass through the body which allows delineating the body structures that do not contain this compound.6

The use of iopodic acid in hyperthyroidism is related to the inhibition of 5'-monodeiodinase type I and II; this will later impair the extrathyroidal conversion of thyroxine (T4) to triiodothyronine (T3).2,3

TargetActionsOrganism
AThyroxine 5-deiodinase
antagonist
Humans
Absorption

The lipophilicity of ipodate is sufficient for passage through the gastrointestinal mucosa.1 After ingestion, iopodic acid is promptly absorbed by passive diffusion in the small intestinal mucosa. The presence of bile salts in the duodenum is essential for its diffusion through the intestine wall and a high-fat diet is important in order to increase the absorption effectivity. The maximum effect is showed to be attained 5 hours after the initial dosage and the effect were retained for more than 60 hours.4

Volume of distribution
Not Available
Protein binding

The absence of a substituent at position 5 allows the compound to bind to serum albumin.1 This is the reason why immediately after absorption, iopanoic acid enters the bloodstream it binds to albumin and it is transported to the liver.4

Metabolism

The absence of a substituent at position 5 facilitates for preferential hepatocyte uptake. Once taken in the liver, the metabolism is mainly performed by glucuronide conjugation in the same pathway as bilirubin.1

Route of elimination

The metabolism products of ipodate are readily excreted into the bile, follow the bile flow to fill up the gallbladder and then excreted by the biliary system in the feces.1 This mode of excretion accounts for 65% of the eliminated dose whereas the kidneys are responsible for the remaining 35% of the elimination.4

Half life
Not Available
Clearance
Not Available
Toxicity

Iopodic acid is cathegorized as one of the top 10 linked to skin reactions.5

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

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Cheng KT: Sodium-2-[(3-butanoylamino-2,4,6-triiodo-phenyl)methyl]butanoate . [PubMed:20641974]
  2. Martino E, Balzano S, Bartalena L, Loviselli A, Sica V, Petrini L, Grasso L, Piga M, Braverman LE: Therapy of Graves' disease with sodium ipodate is associated with a high recurrence rate of hyperthyroidism. J Endocrinol Invest. 1991 Nov;14(10):847-51. doi: 10.1007/BF03347940. [PubMed:1687043]
  3. Chopra IJ, van Herle AJ, Korenman SG, Viosca S, Younai S: Use of sodium ipodate in management of hyperthyroidism in subacute thyroiditis. J Clin Endocrinol Metab. 1995 Jul;80(7):2178-80. doi: 10.1210/jcem.80.7.7608275. [PubMed:7608275]
  4. Braga M, Cooper DS: Clinical review 129: Oral cholecystographic agents and the thyroid. J Clin Endocrinol Metab. 2001 May;86(5):1853-60. doi: 10.1210/jcem.86.5.7484. [PubMed:11344170]
  5. Woo T.M. and Robinson M. (2016). Pharmacotherapeutics for advanced practice nurse prescribers (4th ed.). Davis Company.
  6. Swanson D., et al. (1990). Pharmaceuticals in medical imaging. McGraw-Hill Professional.
  7. FDA Submission [Link]
  8. Up to date [Link]
  9. Radiologyinfo [Link]
  10. Endocrinology association [Link]
External Links
PubChem Compound
5241
PubChem Substance
310265212
ChemSpider
20473670
ChEMBL
CHEMBL3306201
ATC Codes
V08AC08 — Sodium iopodateV08AC10 — Calcium iopodate
MSDS
Download (36.7 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral500 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)168-169ºCChemSrc
boiling point (°C)579.8ºC at 760 mmHgChemSrc
water solubilityInsolubleCheng K. (2005). Molecular imaging and contrast agent database.
logP3.73ChemSrc
pKa4.8Elks. The dictionary of Drugs. (1990)
Predicted Properties
PropertyValueSource
Water Solubility0.00819 mg/mLALOGPS
logP3.59ALOGPS
logP3.4ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)1.99ChemAxon
pKa (Strongest Basic)4.16ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area52.9 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity104.91 m3·mol-1ChemAxon
Polarizability40.23 Å3ChemAxon
Number of Rings1ChemAxon
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 organic compounds known as phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic acid.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Phenylpropanoic acids
Sub Class
Not Available
Direct Parent
Phenylpropanoic acids
Alternative Parents
Iodobenzenes / Aryl iodides / Propargyl-type 1,3-dipolar organic compounds / Monocarboxylic acids and derivatives / Formamidines / Carboxylic acids / Carboxamidines / Organopnictogen compounds / Organoiodides / Organic oxides
show 2 more
Substituents
3-phenylpropanoic-acid / Halobenzene / Iodobenzene / Aryl halide / Aryl iodide / Monocyclic benzene moiety / Benzenoid / Amidine / Formamidine / Carboxylic acid amidine
show 16 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and of T3 (3,5,3'-triiodothyronine) into T2 (3,3'-diiodothyronine). RT3 and T2 are inactive metabolites. May play a role in preventing premature exposure of developing fetal tissues to adult levels of thyroid hormones. Can regulate circulating fetal thyroid hormone concentrations throughout gestation. Essential role for regulation of thyroid hormone inactivation during embryological development.
Specific Function
Thyroxine 5'-deiodinase activity
Gene Name
DIO3
Uniprot ID
P55073
Uniprot Name
Thyroxine 5-deiodinase
Molecular Weight
33947.175 Da
References
  1. Martino E, Balzano S, Bartalena L, Loviselli A, Sica V, Petrini L, Grasso L, Piga M, Braverman LE: Therapy of Graves' disease with sodium ipodate is associated with a high recurrence rate of hyperthyroidism. J Endocrinol Invest. 1991 Nov;14(10):847-51. doi: 10.1007/BF03347940. [PubMed:1687043]
  2. Chopra IJ, van Herle AJ, Korenman SG, Viosca S, Younai S: Use of sodium ipodate in management of hyperthyroidism in subacute thyroiditis. J Clin Endocrinol Metab. 1995 Jul;80(7):2178-80. doi: 10.1210/jcem.80.7.7608275. [PubMed:7608275]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Cheng KT: Sodium-2-[(3-butanoylamino-2,4,6-triiodo-phenyl)methyl]butanoate . [PubMed:20641974]

Drug created on November 24, 2015 12:31 / Updated on July 13, 2019 00:53