Gadodiamide

Identification

Summary

Gadodiamide is a gadolinium-based contrast agent (GBCA) used with contrasted magnetic resonance imaging (MRI) to detect and visualize lesions and abnormal vascularity.

Brand Names
Omniscan
Generic Name
Gadodiamide
DrugBank Accession Number
DB00225
Background

Gadodiamide is a linear, non-ionic gadolinium-based contrast agent (GBCA) that is used in magnetic resonance imaging (MRI) procedures to assist in the visualization of blood vessels.1,2 GBCAs constitute the largest group of MR agents, and they are thought to be safer than nonionic iodinated contrast agents.3 Approved by the FDA in 1993, gadodiamide is the first non-ionic GBCA to be used.4 However, since linear, non-ionic GBCA is less stable than macrocyclic or ionic GBCA, gadodiamide can potentially lead to more gadolinium retention in the brain and thus more likely to cause side effects.5

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 573.66
Monoisotopic: 574.10225
Chemical Formula
C16H26GdN5O8
Synonyms
  • Gadodiamida
  • Gadodiamide
  • Gadodiamide anhydrous
External IDs
  • S-041

Pharmacology

Indication

Gadodiamide is indicated for the visualization of lesions with abnormal vascularity in the brain (intracranial lesions), spine, and associated tissues and the body (including the thoracic (noncardiac), abdominal, pelvic cavities, and retroperitoneal space) by the FDA and Health Canada.7,6 Additionally, gadoliamide is approved by Health Canada to detect and localize tenosis in renal arteries and aorto-iliac arteries in magnetic resonance angiography (MRA).7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Diagnostic agentCns abnormal vascularity•••••••••••••••••• ••••••••••••••••••
Diagnostic agentCns abnormal vascularity•••••••••••••••••••••
Diagnostic agentStenosis•••••••••••••••••••••
Diagnostic agentAbnormal vascularity••••••••••••••••••••••••••
Diagnostic agentAbnormal vascularity•••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

In magnetic resonance imaging, visualization of normal and pathologic tissue depends in part on variations in the radiofrequency signal intensity. These variations occur due to: changes in proton density; alteration of the spin-lattice or longitudinal relaxation time (T1); and variation of the spin-spin or transverse relaxation time (T2). Gadodiamide is a paramagnetic agent with unpaired electron spins which generate a local magnetic field. As water protons move through this local magnetic field, the changes in the magnetic field experienced by the protons reorient them with the main magnetic field more quickly than in the absence of a paramagnetic agent.6

By increasing the relaxation rate, gadodiamide decreases both the T1 and T2 relaxation times in tissues where it is distributed. At clinical doses, the effect is primarily on the T1 relaxation time and produces an increase in signal intensity. Disruption of the blood-brain barrier or abnormal vascularity allows the accumulation of gadodiamide in lesions such as neoplasms, abscesses, and subacute infarcts. The pharmacokinetic parameters of gadodiamide in various lesions are not known.6

Mechanism of action

Gadodiamide paramagnetic molecule that develops a magnetic moment when placed in a magnetic field. The magnetic moment alters the relaxation rates of water protons in its vicinity in the body. Its use in magnetic resonance imaging (MRI) allows to selectively increase contrast in tissues where gadodiamide accumulates.6

Absorption

The pharmacokinetics of intravenously administered gadodiamide in normal subjects conforms to an open, two-compartment model.6

Volume of distribution

The volume of distribution of gadodiamide (200 ± 61 mL/kg) is equivalent to that of extracellular water. Following GBCA administration, gadolinium is present for months or years in the brain, bone, skin, and other organs.6

Protein binding

Gadodiamide does not bind to human serum proteins in vitro.6

Metabolism

There is no detectable biotransformation or decomposition of gadodiamide.

Route of elimination

Gadodiamide is eliminated primarily in the urine with 95.4 ± 5.5% (mean ± SD) of the administered dose eliminated by 24 hours.6

Half-life

The mean distribution and elimination half-lives (reported as mean ± SD) were calculated to be of 3.7 ± 2.7 minutes and 77.8 ± 16 minutes, respectively.6

Clearance

The renal and plasma clearance rates of gadodiamide are nearly identical (1.7 and 1.8 mL/min/kg, respectively), and are similar to that of substances excreted primarily by glomerular filtration.6

Adverse Effects
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Toxicity

GBCAs cross the human placenta and result in fetal exposure and gadolinium retention. The human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive. In animal reproduction studies, no adverse fetal effects were observed with the administration of gadodiamide to pregnant rats during organogenesis at doses 1.3 times the maximum human dose based on body surface area. Because of the potential risks of gadolinium to the fetus, use gadodiamide only if imaging is essential during pregnancy and cannot be delayed.6

Clinical consequences of overdose with gadodiamide have not been reported. The minimum lethal dose of intravenously administered gadodiamide in rats and mice is greater than 20 mmol/kg (200 times the recommended human dose of 0.1 mmol/kg; 67 times the cumulative 0.3 mmol/kg dose). Gadodiamide is dialyzable.6

Long-term animal studies have not been performed to evaluate the carcinogenic potential of gadodiamide. The results of the following genotoxicity assays were negative: in vitro bacterial reverse mutation assay, in vitro Chinese Hamster Ovary (CHO)/Hypoxanthine Guanine Phosphoribosyl Transferase (HGPT) forward mutation assay, in vitro CHO chromosome aberration assay, and the in vivo mouse micronucleus assay at intravenous doses of 27 mmol/kg (approximately 7 times the maximum human dose based on a body surface area comparison). Impairment of male or female fertility was not observed in rats after intravenous administration three times per week at the maximum dose tested of 1.0 mmol/kg (approximately 0.5 times the maximum human dose based on a body surface area comparison).6

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
AbacavirGadodiamide may decrease the excretion rate of Abacavir which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Gadodiamide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Gadodiamide which could result in a higher serum level.
AcetaminophenGadodiamide may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Gadodiamide which could result in a lower serum level and potentially a reduction in efficacy.
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Gadodiamide hydrate0RPE15QPL0122795-43-1WYKPQCVMUQQKCL-UHFFFAOYSA-K
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
OmniscanInjection287 mg/1mLIntravenousGE Healthcare Inc.2002-04-19Not applicableUS flag
OmniscanInjection287 mg/1mLIntravenousGE Healthcare Inc.2006-09-212019-11-30US flag
OmniscanSolution287 mg / mLIntravenousGe Healthcare1997-03-25Not applicableCanada flag
Omniscan Liq IV 287mg/mlLiquid287 mg / mLIntravenousSanofi1994-12-311997-07-30Canada flag

Categories

ATC Codes
V08CA03 — Gadodiamide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid amides
Alternative Parents
Alpha amino acids / Tricarboxylic acids and derivatives / Trialkylamines / Secondary carboxylic acid amides / Carboxylic acid salts / Amino acids / Carboxylic acids / Organopnictogen compounds / Organic zwitterions / Organic salts
show 3 more
Substituents
Aliphatic acyclic compound / Alpha-amino acid / Alpha-amino acid amide / Amine / Amino acid / Carbonyl group / Carboxamide group / Carboxylic acid / Carboxylic acid salt / Hydrocarbon derivative
show 12 more
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
gadolinium coordination entity (CHEBI:37333)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
84F6U3J2R6
CAS number
131410-48-5
InChI Key
HZHFFEYYPYZMNU-UHFFFAOYSA-K
InChI
InChI=1S/C16H29N5O8.Gd/c1-17-12(22)7-20(10-15(26)27)5-3-19(9-14(24)25)4-6-21(11-16(28)29)8-13(23)18-2;/h3-11H2,1-2H3,(H,17,22)(H,18,23)(H,24,25)(H,26,27)(H,28,29);/q;+3/p-3
IUPAC Name
gadolinium(3+) 2-[bis({2-[(carboxylatomethyl)[(methylcarbamoyl)methyl]amino]ethyl})amino]acetate
SMILES
[Gd+3].CNC(=O)CN(CCN(CCN(CC([O-])=O)CC(=O)NC)CC([O-])=O)CC([O-])=O

References

General References
  1. Ichikawa S, Omiya Y, Onishi H, Motosugi U: Linear gadolinium-based contrast agent (gadodiamide and gadopentetate dimeglumine)-induced high signal intensity on unenhanced T(1) -weighted images in pediatric patients. J Magn Reson Imaging. 2019 Apr;49(4):1046-1052. doi: 10.1002/jmri.26311. Epub 2018 Oct 11. [Article]
  2. Aslanian V, Lemaignen H, Bunouf P, Svaland MG, Borseth A, Lundby B: Evaluation of the clinical safety of gadodiamide injection, a new nonionic MRI contrast medium for the central nervous system: a European perspective. Neuroradiology. 1996 Aug;38(6):537-41. doi: 10.1007/BF00626092. [Article]
  3. Runge VM: Safety of approved MR contrast media for intravenous injection. J Magn Reson Imaging. 2000 Aug;12(2):205-13. doi: 10.1002/1522-2586(200008)12:2<205::aid-jmri1>3.0.co;2-p. [Article]
  4. Pierre VC, Allen MJ, Caravan P: Contrast agents for MRI: 30+ years and where are we going? J Biol Inorg Chem. 2014 Feb;19(2):127-31. doi: 10.1007/s00775-013-1074-5. Epub 2014 Jan 11. [Article]
  5. Robert P, Violas X, Grand S, Lehericy S, Idee JM, Ballet S, Corot C: Linear Gadolinium-Based Contrast Agents Are Associated With Brain Gadolinium Retention in Healthy Rats. Invest Radiol. 2016 Feb;51(2):73-82. doi: 10.1097/RLI.0000000000000241. [Article]
  6. FDA Approved Drug Products: OMNISCANTM (gadodiamide) Injection for Intravenous Use (Feb 2024) [Link]
  7. Product Monograph: OMNISCAN (Gadodiamide) Intravenous Injection [Link]
PubChem Compound
24847884
PubChem Substance
46504789
ChemSpider
135661
RxNav
41144
ChEBI
37333
PharmGKB
PA164784027
RxList
RxList Drug Page
Wikipedia
Gadodiamide
MSDS
Download (56.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableChronic Kidney Disease (CKD) / Impaired Renal Function1
4RecruitingOtherCognitive Functioning / Contrast Medium / Motor Function1
4RecruitingSupportive CareNephrogenic Fibrosing Dermopathy1
3CompletedDiagnosticAnatomic renal artery stenosis1
3CompletedDiagnosticAorto-Iliac Stenosis / Arterial Occlusive Diseases1

Pharmacoeconomics

Manufacturers
  • Ge healthcare
Packagers
  • Amersham Health Inc.
  • GE Healthcare Inc.
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous287 mg/ml
InjectionIntravenous
InjectionIntravenous287 mg/1mL
Injection, solutionIntravenous
SolutionIntravenous287 mg / mL
SolutionIntravenous287 mg/1ml
InjectionIntravenous0.5 mmol/ml
Injection, solutionIntravenous0.5 mmol/ml
LiquidIntravenous287 mg / mL
SolutionIntravenous287 mg
SolutionIntravenous28700000 mg
SolutionIntravenous
Prices
Unit descriptionCostUnit
Omniscan prefill plus syringe7.02USD ml
Omniscan 287 mg/ml vial6.98USD ml
Omniscan 287 mg/ml bottle6.49USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5560903No1996-10-012013-10-01US flag
US5362475No1994-11-082011-11-08US flag
CA1335819No1995-06-062012-06-06Canada flag

Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility5.21 mg/mLALOGPS
logP0.02ALOGPS
logP-8.7Chemaxon
logS-2.1ALOGPS
pKa (Strongest Acidic)1.02Chemaxon
pKa (Strongest Basic)8.34Chemaxon
Physiological Charge-2Chemaxon
Hydrogen Acceptor Count11Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area188.31 Å2Chemaxon
Rotatable Bond Count16Chemaxon
Refractivity132.4 m3·mol-1Chemaxon
Polarizability40.47 Å3Chemaxon
Number of Rings0Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.9808
Blood Brain Barrier+0.62
Caco-2 permeable-0.5605
P-glycoprotein substrateSubstrate0.7041
P-glycoprotein inhibitor INon-inhibitor0.9016
P-glycoprotein inhibitor IINon-inhibitor0.9571
Renal organic cation transporterNon-inhibitor0.9031
CYP450 2C9 substrateNon-substrate0.8265
CYP450 2D6 substrateNon-substrate0.8189
CYP450 3A4 substrateNon-substrate0.5872
CYP450 1A2 substrateNon-inhibitor0.9416
CYP450 2C9 inhibitorNon-inhibitor0.9189
CYP450 2D6 inhibitorNon-inhibitor0.9566
CYP450 2C19 inhibitorNon-inhibitor0.8972
CYP450 3A4 inhibitorNon-inhibitor0.9864
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9927
Ames testNon AMES toxic0.8343
CarcinogenicityNon-carcinogens0.8563
BiodegradationNot ready biodegradable0.7604
Rat acute toxicity1.9159 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9582
hERG inhibition (predictor II)Non-inhibitor0.9424
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0229-4329100000-8bd2705c0b6e524d965a
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Drug created at June 13, 2005 13:24 / Updated at February 25, 2024 21:03