Identification

Summary

Ioversol is a diagnostic contrast agent used in various medical imaging procedures, such as angiography, urography, and computed tomographic scans.

Brand Names
Optiray
Generic Name
Ioversol
DrugBank Accession Number
DB09134
Background

Ioversol is a non-ionic compound with a tri-iodinated benzene ring used as a contrast dye in diagnostic procedures to visualize different types of organs and tissues.2 Iodine has a high atomic density, which gives it the ability to attenuate X-rays.4 The intravascular administration of iodine compounds, such as ioversol, enhances the contrast between vessels in the path of the flow of the contrast medium and normal tissue, allowing the visualization of internal structures.2 Ioversol is a highly hydrophilic agent considered to be generally safe4; however, serious adverse reactions have been reported due to the inadvertent intrathecal administration of ioversol, which is only indicated for intra-arterial and intravenous use.2

Ioversol was approved by the FDA in 1989 and is currently indicated for computed tomographic (CT) imaging and contrast enhancement in peripheral arteriography, coronary arteriography, and left ventriculography.2,4

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 807.115
Monoisotopic: 806.86466
Chemical Formula
C18H24I3N3O9
Synonyms
  • Ioversol
  • N,N'-Bis (2,3-dihydroxypropyl)-5-[N-(2-hydroxyethyl) -glycolamido] -2,4,6-triiodoisophthalamide
  • Optiray
External IDs
  • MP 328
  • MP-328
  • MP328

Pharmacology

Indication

As the product Optiray 300, the intra-arterial use of ioversol is indicated for cerebral arteriography and peripheral arteriography in adults, while its intravenous use is indicated for CT imaging of the head and body, venography, and intravenous excretory urography in adults.2

As the product Optiray 320, the intra-arterial use of ioversol is indicated for cerebral arteriography, peripheral arteriography, visceral and renal arteriography, aortography, coronary arteriography, and left ventriculography in adults, and angiocardiography in pediatic patients.2 The intravenous use of this product is indicated for CT imaging of the head and body, venography, and intravenous excretory urography in adults and CT imaging of the head and body, and intravenous excretory urography in pediatric patients.2

As the product Optiray 350, the intra-arterial use of ioversol is indicated for peripheral arteriography coronary arteriography, and left ventriculography in adults, and angiocardiography in pediatic patients.2 The intravenous use of this product is indicated for CT imaging of the head and body, venography, intravenous excretory urography, and intravenous digital subtraction angiography (IV-DSA) in adults and CT imaging of the head and body, and intravenous excretory urography in pediatric patients.2

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Contraindications & Blackbox Warnings
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Pharmacodynamics

The contrast enhancement obtained with ioversol is related to iodine content. Immediately after ioversol is injected, a peak in iodine plasma levels can be detected. However, depending on the organ being imaged, the time to maximum contrast will vary.2 The time to maximum contrast enhancement will range from the time iodine plasma levels reach their highest concentration to one hour after intravenous bolus administration. The delay between a peak in iodine plasma levels and maximum contrast enhancement is partly due to the accumulation of iodine-containing medium within a lesion and outside the blood pool.2

For angiographies, the maximum contrast enhancement of ioversol occurs almost immediately (15-120 seconds). Following rapid intravenous injection, ioversol can be visualized in the renal parenchyma within 30 to 60 seconds. In patients with normal renal function, opacification of the calyces and pelves takes place within 1-3 minutes, with an optimum contrast within 5-15 minutes.2

Mechanism of action

Ioversol is a highly soluble non-ionic ionidated contrast agent. Intravascular injection of ioversol opacifies those vessels in the path of the flow of the contrast medium, allowing the radiographic visualization of the internal structures until significant hemodilution occurs.2 In imaging procedures, ioversol diffuses from the vascular to the extravascular space. In brains with an intact blood-brain barrier, this agent does not diffuse to the extravascular space. However, in patients with a disrupted blood-brain barrier, ioversol accumulates in the interstitial space of the disrupted region.2 As the product Optiray, ioversol enhances computed tomographic imaging through augmentation of radiographic efficiency with the degree of density enhancement directly related to the iodine content in an administered dose.3

Absorption

Healthy volunteers that received 50 and 150 mL of ioversol, had a corresponding Cmax of 1.45 mg/mL and 2.36 mg/mL and a corresponding tmax of 2.0 min and 4.3 min.1 AUC was 1.74 mg⋅hr/mL in healthy volunteers that received 50 mL of ioversol, and 4.43 mg⋅hr/mL in those that received 150 mL.1 The pharmacokinetics of ioversol follow an open two compartment model with first-order elimination.3 Since ioversol is almost completely excreted by the kidney as a parent drug, patients with renal impairment are expected to have a lower elimination rate.2

Volume of distribution

In adults, the volume of distribution of ioversol was 0.26 L/kg body weight, consistent with its extracellular space distribution2.

Protein binding

Ioversol does not bind to serum or plasma proteins.2

Metabolism

Ioversol does not undergo significant metabolism, deiodination or biotransformation.2

Route of elimination

Following intravascular administration, ioversol is excreted mainly through the kidneys.3 Within the first 24 hours, more than 95% of the administered dose is excreted. Urine concentration peaks in the first 2 hours after ioversol is administered.2 Fecal elimination is negligible.3

Half-life

The elimination half-life was 1.5 hr in healthy volunteers (n=12) receiving 50 and 150 mL of ioversol 68%.2 In patients with renal dysfunction, the elimination half-life of ioversol is prolonged.3

Clearance

In healthy volunteers that received 50 mL of ioversol, clearance was 156 mL/min, and in those receiving 150 mL of ioversol, clearance was 185 mL/min.1

Adverse Effects
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Toxicity

Ioversol overdosage causes life-threatening adverse effects, mainly in the pulmonary and cardiovascular system.2 In case of an overdose, treatment must focus on the support of vital functions and the prompt institution of symptomatic therapy.3 The carcinogenic potential of ioversol has not been evaluated, and non-clinical studies suggest that ioversol is not mutagenic and does not affect fertility.2 The LD50 values in mice and rats are 17 g/kg and 15 g/kg respectively. Developmental toxicity studies were carried out in rats (gestation day 7 to 17) and rabbits (gestation day 6 to 18) given ioversol at the following intravenous doses: 0, 0.2, 0.8, and 3.2 g iodine/kg/day. Adverse effects on embryo-fetal development were not detected in either species, while maternal toxicity was detected in rabbits at 0.8, and 3.2 g iodine/kg/day.2

Serious adverse reactions have been reported due to the inadvertent intrathecal administration of iodinated contrast media that are not indicated for intrathecal use such as ioversol. These serious adverse reactions include death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema.2 Caution must be exercised in patients with severely impaired renal function, combined renal and hepatic disease, severe thyrotoxicosis, myelomatosis, or anuria, particularly when large doses are administered.3

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
AbacavirAbacavir may decrease the excretion rate of Ioversol which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Ioversol which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Ioversol which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Ioversol which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Ioversol which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Ioversol which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Ioversol which could result in a higher serum level.
AcrivastineIoversol may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Ioversol which could result in a higher serum level.
Adefovir dipivoxilAdefovir dipivoxil may decrease the excretion rate of Ioversol which could result in a higher serum level.
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Food Interactions
No interactions found.

Products

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International/Other Brands
OPTIRAY 300 (Liebel-Flarsheim) / OPTIRAY 320 (Liebel-Flarsheim) / OPTIRAY 350 (Liebel-Flarsheim)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Optiray 160Injection339 mg/1mLIntravascularMallinckrodt Inc.2007-03-232007-03-23US flag
Optiray 160Solution34 %IntravenousTyco Healthcare1992-12-312010-08-05Canada flag
Optiray 160 (ultraject)Solution34 %IntravascularTyco HealthcareNot applicableNot applicableCanada flag
Optiray 240Injection509 mg/1mLIntra-arterial; IntravenousLiebel-Flarsheim Company LLC2012-03-042021-09-15US flag
Optiray 240Solution51 % w/vIntravascular; SubarachnoidLiebel Flarsheim Company Llc1996-11-20Not applicableCanada flag
Optiray 240 (ultraject)Solution51 % w/vIntravascular; SubarachnoidLiebel Flarsheim Company Llc1996-12-31Not applicableCanada flag
Optiray 240 Inj 240mg/mlLiquid240 mg / mLIntravascularMallinckrodt1992-12-312014-12-10Canada flag
Optiray 300Solution64 % w/vIntravascularLiebel Flarsheim Company Llc1998-03-03Not applicableCanada flag
Optiray 300Injection636 mg/1mLIntra-arterial; IntravenousLiebel-Flarsheim Company LLC2011-10-17Not applicableUS flag
Optiray 300 (ultraject)Solution64 % w/vIntravascularLiebel Flarsheim Company LlcNot applicableNot applicableCanada flag

Categories

ATC Codes
V08AB07 — Ioversol
Drug Categories
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
2-halobenzoic acids and derivatives / 4-halobenzoic acids and derivatives / Anilides / Benzamides / Benzoyl derivatives / Iodobenzenes / Aryl iodides / Vinylogous halides / Tertiary carboxylic acid amides / Secondary alcohols
show 8 more
Substituents
2-halobenzoic acid or derivatives / 4-halobenzoic acid or derivatives / Acylaminobenzoic acid or derivatives / Alcohol / Alkanolamine / Anilide / Aromatic homomonocyclic compound / Aryl halide / Aryl iodide / Benzamide
show 21 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
N3RIB7X24K
CAS number
87771-40-2
InChI Key
AMDBBAQNWSUWGN-UHFFFAOYSA-N
InChI
InChI=1S/C18H24I3N3O9/c19-13-11(17(32)22-3-8(29)5-26)14(20)16(24(1-2-25)10(31)7-28)15(21)12(13)18(33)23-4-9(30)6-27/h8-9,25-30H,1-7H2,(H,22,32)(H,23,33)
IUPAC Name
N1,N3-bis(2,3-dihydroxypropyl)-5-[2-hydroxy-N-(2-hydroxyethyl)acetamido]-2,4,6-triiodobenzene-1,3-dicarboxamide
SMILES
OCCN(C(=O)CO)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I

References

Synthesis Reference

Bailey, AR., et al. (1993). Synthesis of ioversol (U.S. Patent No. 5,489,708). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/74/66/8e/1eddf38cd8cd41/US5489708.pdf

General References
  1. Wilkins RA, Whittington JR, Brigden GS, Lahiri A, Heber ME, Hughes LO: Safety and pharmacokinetics of ioversol in healthy volunteers. Invest Radiol. 1989 Oct;24(10):781-8. doi: 10.1097/00004424-198910000-00011. [Article]
  2. FDA Approved Products: OPTIRAY (ioversol) injection for intravenous use [Link]
  3. FDA approval package: OPTIRAY (ioversol) injection [Link]
  4. Molecular Imaging and Contrast Agent Database (MICAD) [Internet]: Ioversol [Link]
  5. Toronto Research Chemicals: Ioversol SDS [Link]
KEGG Drug
D01555
PubChem Compound
3741
PubChem Substance
310265049
ChemSpider
3610
RxNav
27792
ChEBI
31717
ChEMBL
CHEMBL1200614
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ioversol

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4TerminatedOtherRenal Impairment1
4WithdrawnDiagnosticCoronary Artery Disease (CAD) / Diabetes Mellitus / Renal Impairment1
4WithdrawnOtherHypothyroidism1
1RecruitingTreatmentOsteoarthritis of the Knee1
0CompletedScreeningAcute Myeloid Leukemia (AML) / Leukemia Chronic Myelogenous Leukemia (CML) / Multiple Myeloma (MM) / Myelodysplastic Syndromes (MDS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solution300 MG/ML
Injection, solution320 MG/ML
Injection, solution350 MG/ML
Injection, solutionIntra-arterial; Intravenous160 MG/ML
Injection, solutionIntra-arterial; Intravenous240 MG/ML
Injection, solutionIntra-arterial; Intravenous300 MG/ML
Injection, solutionIntra-arterial; Intravenous320 MG/ML
Injection, solutionIntra-arterial; Intravenous350 MG/ML
SolutionIntravenous741 mg
InjectionIntravascular339 mg/1mL
SolutionIntravenous34 %
SolutionIntravascular34 %
InjectionIntra-arterial; Intravenous509 mg/1mL
SolutionIntravascular; Subarachnoid51 % w/v
LiquidIntravascular240 mg / mL
Injection, solutionParenteral
Injection, solutionIntra-arterial; Intravenous
SolutionIntra-arterial; Intravenous
InjectionIntra-arterial; Intravenous636 mg/1mL
Solution300 mg/1ml
SolutionIntravascular64 % w/v
InjectionIntra-arterial; Intravenous678 mg/1mL
InjectionIntravascular
SolutionIntravascular68 % w/v
Solution320 mg/1ml
InjectionIntra-arterial; Intravenous741 mg/1mL
SolutionIntravascular74 % w/v
Solution350 mg/1ml
InjectionIntravascular741 mg/ml
Injection, solutionIntravascular741 mg/ml
SolutionIntravenous678 mg
Injection
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)180-182°CSDS
water solubilityWater solubleFDA label
logP-2.98Howard, PH. Handbook of Physical Properties of Organic Chemicals, Part 1. CRC Press, 1996. p.1395.
Predicted Properties
PropertyValueSource
Water Solubility1.04 mg/mLALOGPS
logP-3ALOGPS
logP-2.1ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)11.72ChemAxon
pKa (Strongest Basic)-2.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count8ChemAxon
Polar Surface Area199.89 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity144.58 m3·mol-1ChemAxon
Polarizability58.31 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
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 at September 29, 2015 22:11 / Updated at May 21, 2022 00:27