Gadoteric acid

Identification

Summary

Gadoteric acid is a diagnostic contrast agent used with magnetic resonance imaging to provide contrast enhancement for intracranial and spinal lesions with abnormal blood brain barrier or abnormal vascularity, and for whole body imaging.

Brand Names

Dotarem

Generic Name

Gadoteric acid

DrugBank Accession Number

DB09132

Background

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.

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 558.65
Monoisotopic: 559.09135
Chemical Formula: C₁₆H₂₅GdN₄O₈

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
Gadoteric acid
Gd-DOTA

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.

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

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Food Interactions

No interactions found.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Gadoterate meglumine	L0ND3981AG	92943-93-6	RYHQMKVRYNEBNJ-BMWGJIJESA-K

Active Moieties

Name	Kind	UNII	CAS	InChI Key
Gadolinium cation (3+)	ionic	AZV954TZ9N	22541-19-1	RJOJUSXNYCILHH-UHFFFAOYSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Dotarem	Injection	376.9 mg/1mL	Intravenous	Guerbet LLC	2019-09-18	Not applicable
Dotarem	Injection	376.9 mg/1mL	Intravenous	Guerbet LLC	2013-04-26	Not applicable
Dotarem	Injection	376.9 mg/1mL	Intravenous	Guerbet LLC	2013-04-26	Not applicable
Dotarem	Solution	376.9 mg / mL	Intravenous	Guerbet	2017-09-22	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Clariscan	Injection, solution	376.9 mg/1mL	Intravenous	Ge Healthcare	2019-11-01	Not applicable
Gadoterate Meglumine	Injection	376.9 mg/1mL	Intravenous	Fresenius Kabi USA, LLC	2022-06-20	Not applicable
Gadoterate Meglumine	Injection	376.9 mg/1mL	Intravenous	Fresenius Kabi USA, LLC	2022-06-20	Not applicable
Gadoterate Meglumine	Injection	376.9 mg/1mL	Intravenous	Fresenius Kabi USA, LLC	2022-06-20	Not applicable
Gadoterate Meglumine	Injection	376.9 mg/1mL	Intravenous	Fresenius Kabi USA, LLC	2022-06-20	Not applicable
Gadoterate Meglumine	Injection	376.9 mg/1mL	Intravenous	Fresenius Kabi USA, LLC	2022-06-20	Not applicable

Chemical Identifiers

UNII: QVF9Y6955W
CAS number: 72573-82-1
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

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

FDA label

Download (3.85 MB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Diagnostic	Renal Dysfunction	1
4	Completed	Not Available	Arterial Occlusive Diseases	1
4	Completed	Diagnostic	Brain Diseases	1
4	Completed	Diagnostic	Coronary Artery Atherosclerosis / Type 2 Diabetes Mellitus	1
4	Completed	Diagnostic	Impaired Renal Function	1
4	Completed	Diagnostic	Magnetic Resonance Imaging (MRI)	2
4	Completed	Diagnostic	Neoplastic CNS Lesions	1
4	Completed	Diagnostic	Peripheral Arterial Disease (PAD)	1
4	Completed	Diagnostic	Primary Brain Tumors	1
4	Completed	Diagnostic	Transient Severe Arterial Phase Motion	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, solution	Intra-articular	1.397 mg/ml
Injection, solution	Intravenous	376.9 mg/1mL
Injection, solution	Parenteral
Injection	Intravenous
Injection, solution	Intravenous	279.3 mg/ml
Solution	Intravenous	279.3 mg
Injection, solution	Intramuscular
Solution	Intravenous
Injection	Intravenous	376.9 mg/1mL
Injection, solution
Injection, solution	Intravenous
Solution	Intravenous	376.9 mg / mL
Solution	Intravenous	377 mg/1ml
Injection, solution	Parenteral	279.32 mg/ml
Injection, solution	Intravenous	27.932 g/100ml
Injection	Intravenous	27.932 g/100ml
Injection, solution	Intravenous	279.32 mg/ml
Injection, solution	Parenteral	0.5 mmol/ml
Injection, solution		377 mg/1ml

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	12.8 mg/mL	ALOGPS
logP	0.23	ALOGPS
logP	-7.7	ChemAxon
logS	-1.7	ALOGPS
pKa (Strongest Acidic)	0.47	ChemAxon
pKa (Strongest Basic)	10.08	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	12	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	170.65 Å²	ChemAxon
Rotatable Bond Count	8	ChemAxon
Refractivity	128.93 m³·mol^-1	ChemAxon
Polarizability	38.15 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 GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available

Drug created at September 29, 2015 19:58 / Updated at August 09, 2022 10:05

Gadoteric acid

Identification

Structure for Gadoteric acid (DB09132)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra