Gadoteric acid

Identification

Name
Gadoteric acid
Accession Number
DB09132
Type
Small Molecule
Groups
Approved
Description

Gadoteric acid is a macrocycle-structured gadolinium-based MRI contrast agent. It is composed of the organic acid DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) used for its chelating properties, and gadolinium (Gd3+). As a paramagnetic molecule, gadoterate develops a magnetic moment when placed in a magnetic field. This magnetic moment enhances the relaxation rates of water protons in its vicinity, leading to an increase in signal intensity (brightness) of tissues. More specifically, it reduces the T1 relaxation time (and to some extent the T2 and T2* relaxation times) in NMR, which is the source of its clinical utility. Increased signal brightness allows it to be used in imaging of blood vessels and of inflamed or diseased tissue where the blood vessels become 'leaky'.

Gadoteric acid, as the FDA approved product Dotarem, is indicated for intravenous use with magnetic resonance imaging (MRI) in brain (intracranial), spine and associated tissues in adult and pediatric patients (2 years of age and older) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity.

Structure
Thumb
Synonyms
  • [2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl-κ4N1,N4,N7,N10)tetraacetato(3−)]gadolinium
  • DOTA-Gd
  • Gadoterate
  • Gd-DOTA
Product Ingredients
IngredientUNIICASInChI Key
Gadoterate meglumineL0ND3981AG92943-93-6RYHQMKVRYNEBNJ-BMWGJIJESA-K
Active Moieties
NameKindUNIICASInChI Key
Gadolinium cation (3+)ionicAZV954TZ9N22541-19-1RJOJUSXNYCILHH-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DotaremSolution376.9 mgIntravenousGuerbet2017-09-22Not applicableCanada
DotaremInjection376.9 mg/1mLIntravenousGuerbet LLC2013-03-20Not applicableUs
Categories
UNII
QVF9Y6955W
CAS number
72573-82-1
Weight
Average: 558.65
Monoisotopic: 559.09135
Chemical Formula
C16H25GdN4O8
InChI Key
GFSTXYOTEVLASN-UHFFFAOYSA-K
InChI
InChI=1S/C16H28N4O8.Gd/c21-13(22)9-17-1-2-18(10-14(23)24)5-6-20(12-16(27)28)8-7-19(4-3-17)11-15(25)26;/h1-12H2,(H,21,22)(H,23,24)(H,25,26)(H,27,28);/q;+3/p-3
IUPAC Name
gadolinium(3+) ion 2-[4,7-bis(carboxylatomethyl)-10-(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate
SMILES
[Gd+3].OC(=O)CN1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1

Pharmacology

Indication

Gadoteric acid is indicated for intravenous use with magnetic resonance imaging (MRI) in brain (intracranial), spine and associated tissues in adult and pediatric patients (2 years of age and older) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity.

Pharmacodynamics

Gadoterate affects proton relaxation times and consequently the MR signal, and the contrast obtained is characterized by the relaxivity of the gadoterate molecule. The relaxivity values for gadoterate are similar across the spectrum of magnetic field strengths used in clinical MRI (0.2 - 1.5 T). Gadoterate does not cross the intact blood-brain barrier and, therefore, does not enhance normal brain or lesions that have a normal blood-brain barrier, e.g. cysts, mature post-operative scars. However, disruption of the blood-brain barrier or abnormal vascularity allows distribution of gadoterate in lesions such as neoplasms, abscesses, and infarcts.

Mechanism of action

Gadoterate is a paramagnetic molecule that develops a magnetic moment when placed in a magnetic field. The magnetic moment enhances the relaxation rates of water protons in its vicinity, leading to an increase in signal intensity (brightness) of tissues. When placed in a magnetic field, gadoterate shortens the T1 and T2 relaxation times in target tissues.

Absorption
Not Available
Volume of distribution

The volume of distribution at steady state of total gadolinium in normal subjects is 179 and 211 mL/kg in female and male subjects respectively, roughly equivalent to that of extracellular water.

Protein binding

Gadoterate does not undergo protein binding in vitro.

Metabolism

Gadoterate is not known to be metabolized.

Route of elimination

Gadoteric acid is excreted primarily in urine.

Half life

Gadoteric acid demonstrates a mean elimination half-life of about 1.4 hr and 2.0 hr in female and male subjects, respectively.

Clearance

In healthy subjects, the renal and total clearance rates of total gadolinium are comparable (1.27 and 1.74 mL/min/kg in females; and 1.40 and 1.64 mL/min/kg in males, respectively).

Toxicity

The most frequent adverse reactions in clinical studies were nausea, headache, injection site pain, injection site coldness, and burning sensation. Nephrogenic Systemic Fibrosis has occurred in patients with impaired elimination of GBCAs.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetaminophenAcetaminophen may decrease the excretion rate of Gadoteric acid which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Gadoteric acid which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Gadoteric acid which could result in a higher serum level.
Adefovir DipivoxilAdefovir Dipivoxil may decrease the excretion rate of Gadoteric acid which could result in a higher serum level.
AlmotriptanAlmotriptan may decrease the excretion rate of Gadoteric acid which could result in a higher serum level.
AlprazolamAlprazolam may decrease the excretion rate of Gadoteric acid which could result in a higher serum level.
AmantadineAmantadine may decrease the excretion rate of Gadoteric acid which could result in a higher serum level.
AmilorideAmiloride may increase the excretion rate of Gadoteric acid which could result in a lower serum level and potentially a reduction in efficacy.
AmitriptylineGadoteric acid may decrease the excretion rate of Amitriptyline which could result in a higher serum level.
AmlodipineAmlodipine may decrease the excretion rate of Gadoteric acid which could result in a higher serum level.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D08007
PubChem Compound
158536
PubChem Substance
310265047
ChemSpider
139460
ChEBI
73732
ChEMBL
CHEMBL3833326
Drugs.com
Drugs.com Drug Page
Wikipedia
Gadoteric_acid
ATC Codes
V08CA02 — Gadoteric acid
AHFS Codes
  • 36:68.00 — Roentgenography
FDA label
Download (3.85 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableEnd-stage Renal Failure (ESRF)1
1, 2TerminatedDiagnosticKidney Diseases / Renal Insufficiency,Chronic1
3CompletedDiagnosticCentral Nervous System Diseases / Diagnostic Self Evaluation1
3CompletedDiagnosticCerebral Arterial Diseases2
3TerminatedDiagnosticAnatomic renal artery stenosis1
3TerminatedDiagnosticKidney Diseases / Renal Arterial Disease1
4Active Not RecruitingDiagnosticHepatocellular,Carcinoma1
4CompletedNot AvailableArterial Occlusive Diseases1
4CompletedDiagnosticBrain Diseases1
4CompletedDiagnosticImpaired Renal Function1
4CompletedDiagnosticMagnetic Resonance Imaging (MRI)1
4CompletedDiagnosticNeoplastic CNS Lesions1
4CompletedDiagnosticPeripheral Arterial Disease (PAD)1
4CompletedDiagnosticPrimary Brain Tumors1
4CompletedDiagnosticTransient Severe Arterial Phase Motion1
4Not Yet RecruitingDiagnosticContrast Media Allergy1
4Not Yet RecruitingDiagnosticMagnetic Resonance Imaging (MRI)1
4Not Yet RecruitingDiagnosticPulmonary Embolism (PE)1
4RecruitingDiagnosticMenière's Disease1
4RecruitingDiagnosticRenal Dysfunction1
Not AvailableCompletedDiagnosticDoxorubicin Induced Cardiomyopathy / Malignant Neoplasm of Female Breast1
Not AvailableEnrolling by InvitationDiagnosticCoronary Artery Disease / Prophylaxis of cardiomyopathy1
Not AvailableRecruitingNot AvailableAdverse Reaction to Drug / Allergic Reaction to Contrast Media1
Not AvailableRecruitingNot AvailableBrain Diseases1
Not AvailableRecruitingNot AvailableDotarem / Gadolinium / Gadolinium Retention / Magnetic Resonance Imaging (MRI) / MultiHance1
Not AvailableRecruitingDiagnosticIntracranial Neoplasm1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntravenous376.9 mg/1mL
SolutionIntravenous376.9 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility12.8 mg/mLALOGPS
logP0.23ALOGPS
logP-7.7ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)0.47ChemAxon
pKa (Strongest Basic)10.08ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area170.65 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity128.93 m3·mol-1ChemAxon
Polarizability38.15 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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as tetracarboxylic acids and derivatives. These are carboxylic acids containing exactly four carboxyl groups.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Tetracarboxylic acids and derivatives
Direct Parent
Tetracarboxylic acids and derivatives
Alternative Parents
Alpha amino acids / Trialkylamines / Carboxylic acid salts / Amino acids / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organic zwitterions / Organic salts / Organic oxides
show 2 more
Substituents
Tetracarboxylic acid or derivatives / Alpha-amino acid / Alpha-amino acid or derivatives / Amino acid or derivatives / Carboxylic acid salt / Amino acid / Tertiary amine / Tertiary aliphatic amine / Carboxylic acid / Azacycle
show 13 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
gadolinium coordination entity (CHEBI:73732)

Drug created on September 29, 2015 13:58 / Updated on October 16, 2018 08:41