Ioversol

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

Similar Structures

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 C_max of 1.45 mg/mL and 2.36 mg/mL and a corresponding t_max 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.

Drug	Interaction
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Abacavir	Abacavir may decrease the excretion rate of Ioversol which could result in a higher serum level.
Aceclofenac	Aceclofenac may decrease the excretion rate of Ioversol which could result in a higher serum level.
Acemetacin	Acemetacin may decrease the excretion rate of Ioversol which could result in a higher serum level.
Acetaminophen	Acetaminophen may decrease the excretion rate of Ioversol which could result in a higher serum level.
Acetazolamide	Acetazolamide may increase the excretion rate of Ioversol which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acid	Acetylsalicylic acid may decrease the excretion rate of Ioversol which could result in a higher serum level.
Aclidinium	Aclidinium may decrease the excretion rate of Ioversol which could result in a higher serum level.
Acrivastine	Ioversol may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Acyclovir	Acyclovir may decrease the excretion rate of Ioversol which could result in a higher serum level.
Adefovir dipivoxil	Adefovir 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

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Optiray 160	Solution	34 %	Intravenous	Tyco Healthcare	1992-12-31	2010-08-05
Optiray 160	Injection	339 mg/1mL	Intravascular	Mallinckrodt Inc.	2007-03-23	2007-03-23
Optiray 160 (ultraject)	Solution	34 %	Intravascular	Tyco Healthcare	Not applicable	Not applicable
Optiray 240	Injection	509 mg/1mL	Intra-arterial; Intravenous	Liebel-Flarsheim Company LLC	2012-03-04	2021-09-15
Optiray 240	Solution	51 % w/v	Intravascular; Subarachnoid	Liebel Flarsheim Company Llc	1996-11-20	Not applicable
Optiray 240 (ultraject)	Solution	51 % w/v	Intravascular; Subarachnoid	Liebel Flarsheim Company Llc	1996-12-31	Not applicable
Optiray 240 Inj 240mg/ml	Liquid	240 mg / mL	Intravascular	Mallinckrodt	1992-12-31	2014-12-10
Optiray 300	Injection	636 mg/1mL	Intra-arterial; Intravenous	Liebel-Flarsheim Company LLC	2012-03-04	Not applicable
Optiray 300	Solution	64 % w/v	Intravascular	Liebel Flarsheim Company Llc	1998-03-03	Not applicable
Optiray 300 (ultraject)	Solution	64 % w/v	Intravascular	Liebel Flarsheim Company Llc	Not applicable	Not applicable

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

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]
FDA Approved Products: OPTIRAY (ioversol) injection for intravenous use [Link]
FDA approval package: OPTIRAY (ioversol) injection [Link]
Molecular Imaging and Contrast Agent Database (MICAD) [Internet]: Ioversol [Link]
Toronto Research Chemicals: Ioversol SDS [Link]

External Links

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

Phase	Status	Purpose	Conditions	Count
4	Terminated	Other	Impaired Renal Function	1
4	Withdrawn	Diagnostic	Coronary Artery Disease (CAD) / Diabetes Mellitus / Impaired Renal Function	1
4	Withdrawn	Other	Hypothyroidism	1
1	Recruiting	Treatment	Osteoarthritis of the Knee	1
0	Completed	Screening	Acute Myeloid Leukemia / Chronic Myelogenous Leukemia (CML) / Multiple Myeloma (MM) / Myelodysplastic Syndrome	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, solution		300 MG/ML
Injection, solution		320 MG/ML
Injection, solution		350 MG/ML
Injection, solution	Intra-arterial; Intravenous	160 MG/ML
Injection, solution	Intra-arterial; Intravenous	240 MG/ML
Injection, solution	Intra-arterial; Intravenous	300 MG/ML
Injection, solution	Intra-arterial; Intravenous	320 MG/ML
Injection, solution	Intra-arterial; Intravenous	350 MG/ML
Solution	Intravenous	741 mg
Injection	Intravascular	339 mg/1mL
Solution	Intravenous	34 %
Solution	Intravascular	34 %
Injection	Intra-arterial; Intravenous	509 mg/1mL
Solution	Intravascular; Subarachnoid	51 % w/v
Liquid	Intravascular	240 mg / mL
Injection, solution	Parenteral
Injection, solution	Intra-arterial; Intravenous	509 mg/ml
Solution	Intra-arterial; Intravenous
Injection	Intra-arterial; Intravenous	636 mg/1mL
Solution		300 mg/1ml
Solution	Intravascular	64 % w/v
Solution	Intra-arterial; Intravenous	636 mg/ml
Injection	Intra-arterial; Intravenous	678 mg/1mL
Injection	Intravascular
Solution	Intravascular	68 % w/v
Solution		320 mg/1ml
Injection	Intra-arterial; Intravenous	741 mg/1mL
Solution	Intravascular	74 % w/v
Solution		350 mg/1ml
Injection	Intravascular	741 mg/ml
Injection, solution	Intravascular	741 mg/ml
Solution	Intra-arterial; Intravenous	741 mg/ml
Solution	Intravenous	678 mg
Injection

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	180-182°C	SDS
water solubility	Water soluble	FDA label
logP	-2.98	Howard, PH. Handbook of Physical Properties of Organic Chemicals, Part 1. CRC Press, 1996. p.1395.

Predicted Properties

Property	Value	Source
Water Solubility	1.04 mg/mL	ALOGPS
logP	-3	ALOGPS
logP	-2.1	Chemaxon
logS	-2.9	ALOGPS
pKa (Strongest Acidic)	11.72	Chemaxon
pKa (Strongest Basic)	-2.6	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	9	Chemaxon
Hydrogen Donor Count	8	Chemaxon
Polar Surface Area	199.89 Å²	Chemaxon
Rotatable Bond Count	12	Chemaxon
Refractivity	144.58 m³·mol^-1	Chemaxon
Polarizability	58.31 Å³	Chemaxon
Number of Rings	1	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

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Drug created at September 29, 2015 22:11 / Updated at March 22, 2023 23:54

Ioversol

Identification

Structure for Ioversol (DB09134)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra