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Identification
- Summary
Ioxaglic acid is a tri-iodinated benzoate contrast agent used in various radiological procedures including angiography, phlebography, urography, computed tomography (CT), and hysterosalpingography.
- Generic Name
- Ioxaglic acid
- DrugBank Accession Number
- DB09313
- Background
Ioxaglic acid is marketed as Hexabrix. This drug is an ionic tri-iodinated benzoate used as a low-osmolality contrast agent during diagnostic imaging procedures. Like other organic iodine compounds, ioxaglic acid blocks x-rays and is opaque in its appearance on x-ray film, improving the visualization of important structures and organs during angiography, arteriography, arthrography, cholangiography, urography, and computed tomography 7.
Ioxaglic acid has a low osmolarity and is associated with fewer side effects compared to older contrast agents 2.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Ioxaglic acid (DB09313)
- Weight
- Average: 1268.886
Monoisotopic: 1268.56583 - Chemical Formula
- C24H21I6N5O8
- Synonyms
- acido ioxaglico
- Ioxaglic acid
- External IDs
- P-286
Pharmacology
- Indication
This medicinal product is for diagnostic use only in adults and children as a low-osmolality medium 2, 1.
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This drug allows for the visualization of important organs and structures in the body. It binds to tissues, allowing the blockage of X-rays and diagnostic visualization in various soft tissues and body cavities 8.
The joint spaces in addition to the uterus and fallopian tubes may be visualized by the direct injection of the contrast medium into the region to be studied 4.
- Mechanism of action
Ioxaglic acid is an iodine-containing, low osmolality contrast agent 2,3,1. Ioxaglate is a molecule that consists of six iodine atoms and achieves water solubility by ionization; thus, it is a 3.0 ratio ionic agent 6.
By far the most successful and widely used contrast agents in use today are the iodinated contrast media, which were introduced into clinical practice in the 1950s. Approximately 75 million doses of iodinated contrast agents are administered worldwide each year. The iodinated contrast agents fall into 4 groups. Each group has unique chemical, physical, and biologic properties. These various contrast agents are required to meet the demands of a broad variety of imaging modalities 7.
All agents share a similar function group—a tri-iodinated benzene ring. Iodine plays an imperative role in the attenuation of x-ray signal. The atomic radius of a covalently bonded iodine atom is about 133 picometers, falling within the same range of the wavelengths of x-rays: 10 to 10,000 picometers. Therefore, x-rays are easily attenuated by the iodine atoms. In addition, iodine atoms covalently bonded to a benzene ring have 2 main advantages: (1) 3 large atoms located in such close proximity increase the effective molecular size, attenuating longer-wavelength x-rays, and (2) covalent bonding to a stable organic functional group (for example, benzene) decrease the risk of toxic adverse effects from free iodide molecules 7.
Ionization is an important characteristic to note in contrast media preparations 8. Compounds are classified as either ionic or nonionic. The ionic compounds dissociate in aqueous solution and therefore have a higher osmolality. The anion is the radiopaque portion of the molecule, however, both the anion and cation are osmotically active 8. Compared with nonionic media such as ioxaglic acid, ionic contrast media have more adverse hemodynamic effects, especially in patients with heart disease. The nonionic media are water soluble but do not dissociate in solution. Nonionic agents possess lower osmolality because there are fewer particles in solution. The nonionic contrast agents are more hydrophilic than ionic agents, resulting in lower osmolality, reduced binding to plasma proteins, decreased tissue binding, and a decreased tendency to cross cell membranes 8.
The low-osmolality of ioxaglic acid reduces the risk of adverse events. The occurrence of adverse reactions is more common after the use of high-osmolarity agents: about 15% with a high-osmolarity agent versus 3% with a low-osmolarity agent 7.
The use of high-osmolarity agents has decreased significantly in recent years. Most adverse effects and adverse reactions to this group of drugs are multifactorial and are likely due to a combination of direct cellular toxicity, the ionic state (for example, ionic vs nonionic), or the osmolarity of the injected contrast drug 7.
- Absorption
Following the intravascular route of injection, Ioxaglic acid is rapidly transported through the circulatory system to the kidneys.
The pharmacokinetics of radiopaque contrast media given by the IV route are described by a two-compartment model with a rapid alpha phase for drug distribution and a slow beta phase for the elimination of the drug2. Following the intravenous administration of 50 mL of ioxaglic acid in 10 healthy volunteers, the mean peak plasma concentration occurred at two (1-3) minutes, reaching a concentration of 2.1 (1.8-2.8) mg/mL.
Approximately 50 percent of the intravenously administered dose was recovered in the urine at two hours, and 90% percent was recovered at the 24 hour time point 2.
- Volume of distribution
Ioxaglate salts cross the placental barrier in humans and are excreted unchanged in human milk 4.
- Protein binding
Ioxaglic acid binds very weakly to plasma proteins 5 and is quickly eliminated unchanged by the kidneys (glomerular filtration with no re-absorption or tubular secretion).
- Metabolism
Excreted unchanged 5.
- Route of elimination
Excreted unchanged in the urine 2 The liver and small intestine provide the major alternate route of excretion. In patients with severe renal impairment, the excretion of this contrast medium through the gallbladder and into the small intestine sharply increases 4.
- Half-life
Hexabrix 320 is rapidly eliminated by the kidneys with a half-life of about 90 minutes 3
- Clearance
245 ml/kg 5
- Adverse Effects
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Adverse reactions after administration of iodinated contrast agents may be worsened in patients displaying agitation, anxiety, and pain. Appropriate management, such as sedation, may be required before the procedure 2. Adequate hydration and normal electrolyte balance must be ensured, especially in elderly patients, infants, small children, patients with renal damage (oliguria, polyuria) or hyperuricemia, multiple myeloma, patients diagnosed with plasmacytoma or diabetes mellitus, particularly if it is longstanding 2.
As this drug is a contrast agent, it may cause minor or major reactions that may be serious or lethal 2. They may be rapid (within 60 minutes) or delayed (up to 1 week) 2.
Emergency measures must be immediately available in high risk individuals, especially in patients taking B-blockers in whom adrenaline and vascular perfusion would not be effective 2.
There are several conditions in which caution must be observed while administering this contrast drug 2:
Renal Disease/Hepatic Disease
Particular attention is required if the patient has both hepatic and renal failure, which increases the risk of contrast agent retention 2.
Cardiovascular Disease In patients with manifest or incipient heart failure, coronary disease, pulmonary hypertension, or valvular heart disease, the risks of pulmonary edema, myocardial ischemia and arrhythmia and severe hemodynamic disturbances is heightened after the administration of an iodinated contrast agent.
Cases of Torsade de Pointes have been identified in patients using sodium and meglumine ioxaglate, therefore loxaglic acid should be administered very carefully to patients who have/may develop prolongation of QTc, including patients taking other medicines that contribute to cardiovascular QT prolongation 2.
Pheochromocytoma Patients
Patients with phaeochromocytoma may suddenly develop hypertension after intravascular administration of a contrast agent, which may require appropriate management before the examination 2
Thyroid Disease
Following injection of iodinated contrast agent, specifically in patients with goiter or a history of hypothyroidism, there is a risk of either an episode of hyperthyroidism or induction of a new episode of hypothyroidism.
There is also a risk of hypothyroidism in newborns who have received, or whose mother has received, an iodinated contrast agent.
Screening for hypothyroidism should be performed routinely after administration of the product to newborns and judiciously to premature babies by assaying TSH and possibly free T4, 7-10 days and 1 month after iodine overload 2.
Asthma
Asthma should be controlled before injecting the iodinated contrast agent 2.
Particular attention is required if the asthmatic attack has occurred within eight days prior to administration of loxagic acid, because of the increased risk for bronchospasm.
Myasthenia gravis
Administration of a contrast agent may exacerbate the symptoms of myasthenia gravis 2.
Use in pregnancy
In the patient screening and with appropriate tests, it is advisable to identify possible pregnancy in women of childbearing age. Exposure of the female genital tract to x-rays warrants careful evaluation of the benefit-to-risk ratio 2.
- 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.Not Available
- Food Interactions
- Take separate from meals. Individuals may need to avoid eating before some procedures where ioxaglic acid is used.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Ioxaglate meglumine 75JR975T11 59018-13-2 HUHDYASLFWQVOL-WZTVWXICSA-N Ioxaglate sodium HQ43CN02U9 67992-58-9 MBVDCEVFLAONHO-UHFFFAOYSA-M - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Hexabrix Ioxaglate meglumine (393 mg/1mL) + Ioxaglate sodium (196 mg/1mL) Injection Intravascular Mallinckrodt 1985-07-26 2015-09-30 US 
Hexabrix Ioxaglate meglumine (393 mg/1mL) + Ioxaglate sodium (196 mg/1mL) Injection Intravascular Guerbet 2009-04-09 2015-09-30 US Hexabrix Ioxaglate meglumine (393 mg/1mL) + Ioxaglate sodium (196 mg/1mL) Injection Intravascular Mallinckrodt 1985-07-26 2015-09-30 US Hexabrix Ioxaglate meglumine (393 mg/1mL) + Ioxaglate sodium (196 mg/1mL) Injection Intravascular Guerbet 2009-04-09 2015-09-30 US Hexabrix 200 Ioxaglate sodium (123 mg / mL) + Ioxaglate meglumine (246 mg / mL) Solution Intravascular Guerbet 1988-12-31 2015-07-08 Canada 
Categories
- ATC Codes
- V08AB03 — Ioxaglic acid
- Drug Categories
- Acids, Carbocyclic
- Benzene Derivatives
- Benzoates
- Compounds used in a research, industrial, or household setting
- Contrast Media
- Diagnostic Uses of Chemicals
- Iodobenzoates
- Radiographic Contrast Agent
- Triiodobenzoic Acids
- Watersoluble, Nephrotropic, Low Osmolar X-Ray Contrast Media
- X-Ray Contrast Activity
- X-Ray Contrast Media, Iodinated
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as acylaminobenzoic acid and derivatives. These are derivatives of amino benzoic acid derivatives where the amine group is N-acylated.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzoic acids and derivatives
- Direct Parent
- Acylaminobenzoic acid and derivatives
- Alternative Parents
- Hippuric acids and derivatives / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / P-haloacetanilides / O-haloacetanilides / Halobenzoic acids / 2-halobenzoic acids / 4-halobenzoic acids / Benzoic acids / Benzoyl derivatives show 16 more
- Substituents
- 1-carboxy-2-haloaromatic compound / 2-halobenzoic acid / 2-halobenzoic acid or derivatives / 4-halobenzoic acid / 4-halobenzoic acid or derivatives / Acetamide / Acetanilide / Acylaminobenzoic acid or derivatives / Alcohol / Alkanolamine show 39 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- organoiodine compound, benzoic acids, benzenedicarboxamide (CHEBI:31718)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Z40X7EI2AF
- CAS number
- 59017-64-0
- InChI Key
- TYYBFXNZMFNZJT-UHFFFAOYSA-N
- InChI
- InChI=1S/C24H21I6N5O8/c1-7(37)35(3)20-17(29)10(21(39)31-2)13(25)11(18(20)30)23(41)33-6-8(38)34-19-15(27)9(22(40)32-4-5-36)14(26)12(16(19)28)24(42)43/h36H,4-6H2,1-3H3,(H,31,39)(H,32,40)(H,33,41)(H,34,38)(H,42,43)
- IUPAC Name
- 3-[(2-hydroxyethyl)carbamoyl]-2,4,6-triiodo-5-(2-{[2,4,6-triiodo-3-(methylcarbamoyl)-5-(N-methylacetamido)phenyl]formamido}acetamido)benzoic acid
- SMILES
- CNC(=O)C1=C(I)C(C(=O)NCC(=O)NC2=C(I)C(C(O)=O)=C(I)C(C(=O)NCCO)=C2I)=C(I)C(N(C)C(C)=O)=C1I
References
- General References
- Meijenhorst GC, de Bruin JN: Hexabrix (ioxaglate), a new low osmolality contrast agent for lumbar epidural double-catheter venography. Neuroradiology. 1980 Aug;20(1):29-32. [Article]
- Loxaglic acid [Link]
- Ioxaglic acid, NZ MedSAFE Data sheet [Link]
- FDA letter, Ioxaglic Acid [Link]
- HEXABRIX 320 (320 mg I/ml), solution for injection [Link]
- Are low osmolality contrast media less neprotoxic? [Link]
- Clinical Pharmacology, Uses, and Adverse Reactions of Iodinated Contrast Agents: A Primer for the Non-radiologist [Link]
- Imaging-related medications: a class overview [Link]
- External Links
- KEGG Drug
- D01761
- PubChem Compound
- 3742
- PubChem Substance
- 310265198
- ChemSpider
- 3611
- 1426458
- ChEBI
- 31718
- ChEMBL
- CHEMBL1201291
- Wikipedia
- Ioxaglic_acid
- MSDS
- Download (497 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Completed Not Available Coronary Artery Disease (CAD) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravascular Injection, solution Intravascular 320 mg/100ml Injection, solution Parenteral 320 MG/ML Solution Intravascular Injection Intravascular 39.3 g Injection Intravascular; Intravenous 320 mg I/ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) >254°C MSDS water solubility soluble https://www.whocc.no/atc_ddd_index/?code=V08AB - Predicted Properties
Property Value Source Water Solubility 0.0152 mg/mL ALOGPS logP 0.58 ALOGPS logP 3.75 Chemaxon logS -4.9 ALOGPS pKa (Strongest Acidic) 2.13 Chemaxon pKa (Strongest Basic) -1.7 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 194.24 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 214.05 m3·mol-1 Chemaxon Polarizability 82.94 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 277.44266 predictedDeepCCS 1.0 (2019) [M+H]+ 279.76773 predictedDeepCCS 1.0 (2019) [M+Na]+ 285.50815 predictedDeepCCS 1.0 (2019)
Drug created at November 16, 2015 22:25 / Updated at June 02, 2024 21:55