Identification
- Summary
Gadoteric acid is a gadolinium-based contrast agent (GBCA) used with contrasted magnetic resonance imaging (MRI) to detect and visualize lesions and abnormal vascularity.
- Brand Names
- Dotarem
- Generic Name
- Gadoteric acid
- DrugBank Accession Number
- DB09132
- Background
Gadoteric acid, commonly used in the salt form gadoterate meglumine, is a macrocyclic, ionic gadolinium-based contrast agent (GBCA).1 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+).2 Gadoterate meglumine has one of the highest thermodynamic stability, apparent stability, and kinetic stability, partly due to its macrocyclic structure, and thus has a more favorable safety profile due to a decreased tendency of gadolinium dechelation.3,4
Gadoterate is approved by the FDA under the brand name DOTAREM on 20th March 2013 for intravenous uses with magnetic resonance imaging (MRI) in the 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.7
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Gadoteric acid (DB09132)
- 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 the brain (intracranial), spine, and associated tissues in adult and pediatric patients (including term neonates) to detect and visualize areas with disruption of the blood-brain barrier (BBB) and/or abnormal vascularity.5
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Diagnostic agent Cns abnormal vascularity •••••••••••• •••••• ••••••••• ••••••••• ••••••••• - Contraindications & Blackbox Warnings
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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). Disruption of the blood-brain barrier or abnormal vascularity allows the distribution of gadoterate in lesions such as neoplasms, abscesses, and infarcts.5
- 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.5
In magnetic resonance imaging (MRI), visualization of normal and pathological tissue depends in part on variations in the radiofrequency signal intensity that occur with differences in proton density, spin-lattice or longitudinal relaxation times (T1), and differences in the spin-spin or transverse relaxation time (T2). When placed in a magnetic field, gadoterate shortens the T1 and T2 relaxation times in target tissues. At recommended doses, the effect is observed with greatest sensitivity in the T1-weighted sequences.5
- Absorption
Within the studied dose range (0.1 to 0.3 mmol/kg), the kinetics of total gadolinium appear to be linear.5
Following the administration of 0.1 mmol/kg of gadoterate meglumine in healthy volunteers, the Cmax, Tmax, AUC0-t, and AUC0-∞ were measured to be 799.03 (192.63) µmol/L, 5.00 (0.10-10.00) min, 953.51 (76.22) µmolh/L, and 970.72 (73.34) µmolh/L for female and 836.85 (451.02) µmol/L, 5.00 (0.11-10.00) min, 1038.74 (240.46) µmolh/L, and 1061.16 (239.24) µmolh/L for male subjects respectively.6
- Volume of distribution
The volume of distribution at steady state of total gadolinium in healthy subjects is 179 ± 26 and 211 ± 35 mL/kg in female and male subjects respectively, roughly equivalent to that of extracellular water. The extent of blood cell partitioning of gadoterate is not known.5
- Protein binding
Gadoterate does not undergo protein binding in vitro.5
- Metabolism
Gadoterate is not known to be metabolized.5
- Route of elimination
Following a 0.1 mmol/kg dose of gadoterate, total gadolinium is excreted primarily in the urine with 72.9 ± 17.0% and 85.4 ± 9.7% (mean ± SD) eliminated within 48 hours, in female and male subjects, respectively. Similar values were achieved after a cumulative dose of 0.3 mmol/kg (0.1 + 0.2 mmol/kg, 20 minutes later), with 85.5 ± 13.2% and 92.0 ± 12.0% recovered in urine within 48 hrs in female and male subjects respectively.5
- Half-life
Following an intravenously administered 0.1 mmol/kg, gadoterate demonstrates a mean elimination half-life of about 1.4 ± 0.2 hr and 2.0 ± 0.7 hr in female and male subjects, respectively.L49911]
- Clearance
In healthy subjects, the renal and total clearance rates of total gadolinium are comparable (1.27 ± 0.32 and 1.74 ± 0.12 mL/min/kg in females; and 1.40 ± 0.31 and 1.64 ± 0.35 mL/min/kg in males, respectively) indicating that the drug is primarily cleared through the kidneys.5
- Adverse Effects
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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, there were no adverse developmental effects observed in rats or rabbits with intravenous administration of gadoterate meglumine during organogenesis at doses of 16 and 10 times, respectively, the recommended human dose. Because of the potential risks of gadolinium to the fetus, use gadoterate only if imaging is essential during pregnancy and cannot be delayed.5
Gadoterate administered to healthy volunteers and to adult patients at cumulative doses up to 0.3 mmol/kg was tolerated in a manner similar to lower doses. Adverse reactions to overdosage with gadoterate have not been reported. Gadoterate can be removed from the body by hemodialysis.5
Long-term animal studies have not been performed to evaluate the carcinogenic potential of gadoterate meglumine.5
Gadoterate meglumine did not demonstrate mutagenic potential in in vitro bacterial reverse mutation assays (Ames test) using Salmonella typhimurium, in an in vitro chromosome aberration assay in Chinese hamster ovary cells, in an in vitro gene mutation assay in Chinese hamster lung cells, nor in an in vivo mouse micronucleus assay.5
No impairment of male or female fertility and reproductive performance were observed in rats after intravenous administration of gadoterate meglumine at the maximum tested dose of 10 mmol/kg/day (16 times the maximum human dose based on surface area), given during more than 9 weeks in males and more than 4 weeks in females. Sperm counts and sperm motility were not adversely affected by treatment with the drug.5
Local intolerance reactions, including moderate irritation associated with infiltration of inflammatory cells were observed after perivenous injection in rabbits suggesting the possibility of local irritation if the contrast medium leaks around the veins in a clinical setting.
Toxicity of gadoterate meglumine was evaluated in neonatal and juvenile (pre- and post-weaning) rats following a single or repeated intravenous administration at doses 1, 2, and 4 times the MHD based on BSA. Gadoterate meglumine was well tolerated at all dose levels tested and had no effect on growth, pre-weaning development, behavior, or sexual maturation.
- 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 Integrate drug-drug
interactions in your softwareAbacavir 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. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- 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 Region Image Dotarem Injection 376.9 mg/1mL Intravenous Guerbet LLC 2013-03-20 Not applicable US 
Dotarem Injection 376.9 mg/1mL Intravenous Guerbet LLC 2019-09-18 Not applicable US Dotarem Injection 376.9 mg/1mL Intravenous Guerbet LLC 2013-03-20 Not applicable US Dotarem Solution 376.9 mg / mL Intravenous Guerbet 2017-09-22 Not applicable Canada 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Clariscan Injection, solution 376.9 mg/1mL Intravenous Ge Healthcare 2019-11-01 Not applicable US Gadoterate Meglumine Injection 376.9 mg/1mL Intravenous Fresenius Kabi USA, LLC 2022-06-20 Not applicable US Gadoterate Meglumine Injection 376.9 mg/1mL Intravenous Fresenius Kabi USA, LLC 2022-06-20 Not applicable US Gadoterate Meglumine Injection 376.9 mg/1mL Intravenous Fresenius Kabi USA, LLC 2022-06-20 Not applicable US Gadoterate Meglumine Injection 376.9 mg/1mL Intravenous Fresenius Kabi USA, LLC 2022-06-20 Not applicable US
Categories
- ATC Codes
- V08CA02 — Gadoteric acid
- Drug Categories
- Alcohols
- Amino Sugars
- Carbohydrates
- Chelating Agents
- Compounds used in a research, industrial, or household setting
- Contrast Media
- Diagnostic Uses of Chemicals
- Drugs that are Mainly Renally Excreted
- Gadolinium-based Contrast Agent
- Hexosamines
- Magnetic Resonance Imaging Contrast Media
- Other Diagnostics
- Paramagnetic Contrast Media
- Sequestering Agents
- Sugar Alcohols
- Chemical TaxonomyProvided by Classyfire
- 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
- Aliphatic heteromonocyclic compound / Alpha-amino acid / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Azacycle / Carbonyl group / Carboxylic acid / Carboxylic acid salt show 13 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- gadolinium coordination entity (CHEBI:73732)
- Affected organisms
- Not Available
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
- Fallenberg EM, Renz DM, Karle B, Schwenke C, Ingod-Heppner B, Reles A, Engelken FJ, Huppertz A, Hamm B, Taupitz M: Intraindividual, randomized comparison of the macrocyclic contrast agents gadobutrol and gadoterate meglumine in breast magnetic resonance imaging. Eur Radiol. 2015 Mar;25(3):837-49. doi: 10.1007/s00330-014-3426-0. Epub 2014 Sep 25. [Article]
- Xiao Y, Xue R, You T, Li X, Pei F, Wang X, Lei H: Gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugate of arabinogalactan as a potential liver-targeting magnetic resonance imaging contrast agent. Carbohydr Res. 2014 Aug 18;395:9-14. doi: 10.1016/j.carres.2014.05.022. Epub 2014 Jun 6. [Article]
- Ishiguchi T, Takahashi S: Safety of gadoterate meglumine (Gd-DOTA) as a contrast agent for magnetic resonance imaging: results of a post-marketing surveillance study in Japan. Drugs R D. 2010;10(3):133-45. doi: 10.2165/11539140-000000000-00000. [Article]
- 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]
- FDA Approved Drug Products: DOTAREM® (gadoterate meglumine) Injection for intravenous us [Link]
- GADOTERATE CLINICAL PHARMACOLOGY NDA REVIEW [Link]
- Gadoterate Clinical Pharmacology Review [Link]
- 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 Completed Not Available Arterial Occlusive Diseases 1 4 Completed Diagnostic Brain Disorders 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
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 Intravenous 0.5 mmol/mL Injection, solution Intravenous 279.3 mg/ml Solution Intravenous 279.3 mg Injection, solution Intramuscular 0.5 mmol/ml Injection, solution Intramuscular Solution Intravenous 0.5 mmol/ml Injection Intravenous 376.9 mg/1mL Injection, solution Injection, solution 0.5 MMOL/ML Injection, solution 00025 MMOL/ML Injection, solution Intravenous Solution Intravenous 376.9 mg / mL Solution Intravenous 377 mg/1ml Injection, solution Parenteral 279.32 mg/ml Injection, solution Intravenous 0.5 mmol/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
- Liquid
- 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 splash10-052b-6019000000-3ef5221af748627b46a8 - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Drug created at September 29, 2015 19:58 / Updated at April 18, 2024 09:15