Identification
- Summary
Gadoteridol is a gadolinium-based contrast agent (GBCA) used with contrasted magnetic resonance imaging (MRI) to detect and visualize lesions and abnormal vascularity.
- Brand Names
- Prohance
- Generic Name
- Gadoteridol
- DrugBank Accession Number
- DB00597
- Background
Gadoteridol is a macrocyclic nonionic gadolinium that provides contrast enhancement of the brain, spine, and surrounding tissues, resulting in improved visualization (compared with unenhanced MRI) of lesions with abnormal vascularity or those thought to disrupt the normal blood-brain barrier.1,2,4 It was 1 of the 3 macrocyclic gadolinium-based contrast agents (GBCAs) that was mandated by the EMA to replace linear gadolinium-based contrast agents due to concerns about retained gadolinium in the brain.1
Initially approved by the FDA in 1992, gadoteridol received additional approval in 2020 for use in pediatric patients less than 2 years old.5
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Gadoteridol (DB00597)
- Weight
- Average: 558.68
Monoisotopic: 559.127724835 - Chemical Formula
- C17H29GdN4O7
- Synonyms
- gadolinium 2,2',2''-[10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl]triacetate
- gadolinium-HP-DO3A
- Gadoteridol
- Gadoteridolum
- GD-HP-DO 3A
- Gd-HPDO3A
- External IDs
- Gd-HP-DO 3A
- SQ 32692
Pharmacology
- Indication
Gadoteridol is indicated for use with magnetic resonance imaging (MRI) in order to visualize lesions with disrupted blood-brain barrier and/or abnormal vascularity in the brain, spine, and associated tissues in adult and pediatric patients, including term neonates.4 It is also indicated for visualization of lesions in the head and neck in adult patients.4
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Diagnostic agent Cns abnormal vascularity •••••••••••• •••••• ••••••••• ••••••••• ••••••••• Diagnostic agent Central nervous system lesion •••••••••••• •••••• ••••••••• ••••••••• ••••••••• Diagnostic agent Lesions of the head and neck •••••••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
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Gadoteridol affects proton relaxation times and consequently the MR signal. Signal intensity is affected by the dose and relaxivity of the gadoteridol molecule. Consistently, for all gadolinium-based contrast agents, the relaxivity of gadoteridol decreases with the increase of the magnetic field strength used in clinical MRI (0.2 –3.0T).4
Disruption of the blood-brain barrier or abnormal vascularity allows the accumulation of gadoteridol in lesions such as neoplasms, abscesses, and subacute infarcts. The pharmacokinetics of gadoteridol in various lesions is not known.4
- Mechanism of action
Gadoteridol is a paramagnetic agent and, as such, develops a magnetic moment when placed in a magnetic field. The relatively large magnetic moment produced by the paramagnetic agent results in a relatively large local magnetic field, which can enhance the relaxation rates of water protons in the vicinity of the paramagnetic agent.4
In MRI, visualization of normal and pathologic brain tissue depends, in part, on variations in the radiofrequency signal intensity that occur with: 1) differences in proton density; 2) differences of the spinlattice or longitudinal relaxation times (T1); and 3) differences in the spin-spin or transverse relaxation time (T2). When placed in a magnetic field, gadoteridol decreases T1 relaxation times in the target tissues. At recommended doses, the effect is observed with greatest sensitivity in the T1-weighted sequences.4
- Absorption
From population PK model of pediatric subjects receiving a single intravenous dose of 0.1 mmol/kg of gadoteridol, the mean Cmax was 0.66 ± 0.21 mmol/L in pediatric subjects 2 years to 6 years of age, 0.58 ± 0.06 mmol/L in pediatric subjects 6 years to 12 years of age, and 0.68 ± 0.12 mmol/L in adolescent subjects older than 12 years. The mean AUC0-∞ was 0.74 ± 0.20 mmol/Lh in pediatric subjects 2 years to 6 years of age, 0.74 ± 0.09 mmol/Lh in pediatric subjects 6 years to 12 years of age, and 0.98 ± 0.09 mmol/L*h in adolescent subjects older than 12 years of age. Pharmacokinetic simulations indicate similar half-life, AUC, and Cmax values for ProHance in pediatric subjects less than 2 years of age when compared to those reported for adults.4
- Volume of distribution
The plasma distribution volume (mean ± SD) for the non-renally impaired adults was 0.205 ± 0.025 L/kg.Following GBCA administration, gadolinium is present for months or years in the brain, bone, skin, and other organs. 4
- Protein binding
It is unknown if protein binding of gadoteridol occurs in vivo.4
- Metabolism
It is unknown if biotransformation or decomposition of gadoteridol occurs in vivo.4
- Route of elimination
Gadoteridol is eliminated in the urine with 94.4 ± 4.8% (mean ± SD) of the dose excreted within 24 hours post-injection. Over 80% of the dose was recovered in urine for pediatric subjects after 10 hours.4
In patients with moderately and severely impaired renal function about 97% and 76% of the administered dose was recovered in the urine within 7 days and 14 days, respectively.4
- Half-life
The elimination half-life (mean ± SD) is about 1.57 ± 0.08 hours.4
From population PK model of pediatric subjects receiving a single intravenous dose of 0.1 mmol/kg of gadoteridol, the mean distribution half-life (t1/2,alpha) was 0.14 ± 0.04 hours in pediatric subjects 2 years to 6 years of age, 0.18 ± 0.07 hours in pediatric subjects 6 years to 12 years of age, and 0.20 ± 0.07 hours in adolescent subjects older than 12 years of age. The mean elimination half-life (t1/2,beta) was 1.32 ± 0.006 hours in pediatric subjects 2 years to 6 years, 1.32 ± 0.07 hours in pediatric subjects 6 years to 12 years of age, and 1.61 ± 0.19 hours in adolescent subjects older than 12 years of age. Pharmacokinetic simulations indicate similar half-life values for gadoteridol in pediatric subjects less than 2 years of age when compared to those reported for adults.4
In patients with impaired renal function, the serum half-life of gadoteridol is prolonged. After intravenous injection of 0.1 mmol/kg, the elimination half-life of gadoteridol was 10.65 ± 0.06 hours in mild to moderately impaired patients (creatinine clearance 30 to 60 mL/min) and 9.10±0.26 hours in severely impaired patients not on dialysis (creatinine clearance 10 to 30 mL/min).4
- Clearance
The renal and plasma clearance rates (1.41 ± 0.33 mL/ min/kg and 1.50 ± 0.35 mL/ min/kg, respectively) of gadoteridol are essentially identical, indicating no alteration in elimination kinetics on passage through the kidneys and that the drug is essentially cleared through the kidney.4
The mean serum clearance of gadoteridol in patients with normal renal function was 116.14 ± 26.77 mL/min, compared to 37.2 ± 16.4 mL/min in patients with mild to moderate renal impairment and 16.0 ± 3.0 mL/min in patients with severe renal impairment.4
- Adverse Effects
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Gadolinium-based contrast agents (GBCAs) cross the 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. Because of the potential risks of gadolinium to the fetus, use gadoteridol only if imaging is essential during pregnancy and cannot be delayed.4
In animal reproduction studies in rats, gadoteridol doubled the incidence of post-implantation loss at up to 16 times the recommended human dose (RHD). There were no adverse developmental effects observed in rabbits with intravenous administration of gadoteridol during organogenesis at doses up to 19 times the recommended human dose of 0.1 mmol/kg.4
Clinical consequences of overdose with gadoteridol have not been reported. The safety of gadoteridol has been tested in clinical studies using doses up to 0.3 mmol/kg and no clinical consequences related to increasing dose have been observed to date. Gadoteridol can be removed by hemodialysis.4
No animal studies have been performed to evaluate the carcinogenic potential of gadoteridol.4
No changes in reproductive performance and outcome of pregnancy were caused in rats and rabbits by daily intravenous administration of gadoteridol to parent animals before and during gestation up to 1.5 mmol/kg/day (15 times the recommended human dose).4
Gadoteridol did not demonstrate genotoxic activity in: bacterial reverse mutation assays using Salmonella typhimurium and Escherichia coli; a mouse lymphoma forward mutation assay; an in vitro cytogenetic assay measuring chromosomal aberration frequencies in Chinese hamster ovary cells; and an in vivo mouse micronucleus assay at intravenous doses up to 5.0 mmol/kg.4
- 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 Gadoteridol may decrease the excretion rate of Abacavir which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Gadoteridol which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Gadoteridol which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Gadoteridol which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Gadoteridol 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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image ProHance Injection, solution 279.3 mg/1mL Intravenous Bracco Diagnostics Inc 2003-10-09 Not applicable US 
ProHance Injection, solution 279.3 mg/1mL Intravenous BIPSO GmbH 1992-11-16 2016-11-09 US Prohance - Liq IV 279.3mg/ml Solution 279.3 mg / mL Intravenous Bracco Imaging S.P.A. 1998-09-08 Not applicable Canada 
Prohance Liq IV 279.3mg/ml Liquid 279.3 mg / mL Intravenous Squibb Diagnostics, Division Of Bristol Myers Squibb Canada Inc. 1993-12-31 1998-07-30 Canada
Categories
- ATC Codes
- V08CA04 — Gadoteridol
- Drug Categories
- Compounds used in a research, industrial, or household setting
- Contrast Media
- Diagnostic Uses of Chemicals
- Drugs that are Mainly Renally Excreted
- Elements
- Lanthanoid Series Elements
- Magnetic Resonance Contrast Activity
- Magnetic Resonance Imaging Contrast Media
- Metals
- Metals, Rare Earth
- Other Diagnostics
- Paramagnetic Contrast Agent
- Paramagnetic Contrast Media
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alpha amino acids. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon).
- 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 acids
- Alternative Parents
- Tricarboxylic acids and derivatives / Trialkylamines / Secondary alcohols / Carboxylic acid salts / Amino acids / 1,2-aminoalcohols / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organic zwitterions show 4 more
- Substituents
- 1,2-aminoalcohol / Alcohol / Aliphatic heteromonocyclic compound / Alpha-amino acid / Amine / Amino acid / Azacycle / Carbonyl group / Carboxylic acid / Carboxylic acid salt show 14 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- gadolinium coordination entity (CHEBI:31643)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 0199MV609F
- CAS number
- 120066-54-8
- InChI Key
- DPNNNPAKRZOSMO-UHFFFAOYSA-K
- InChI
- InChI=1S/C17H32N4O7.Gd/c1-14(22)10-18-2-4-19(11-15(23)24)6-8-21(13-17(27)28)9-7-20(5-3-18)12-16(25)26;/h14,22H,2-13H2,1H3,(H,23,24)(H,25,26)(H,27,28);/q;+3/p-3
- IUPAC Name
- gadolinium(3+) 2-[4,7-bis(carboxylatomethyl)-10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate
- SMILES
- [Gd+3].CC(O)CN1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1
References
- General References
- Del Poggio A, Anello G, Calloni SF, Vezzulli P, Pereira C, Iadanza A, Falini A, Anzalone N: Diagnostic efficacy and safety of gadoteridol compared to gadobutrol and gadoteric acid in a large sample of CNS MRI studies at 1.5T. J Neuroradiol. 2022 Jan;49(1):73-79. doi: 10.1016/j.neurad.2020.06.005. Epub 2020 Jun 27. [Article]
- Gutierrez JE, Rosenberg M, Seemann J, Breuer J, Haverstock D, Agris J, Balzer T, Anzalone N: Safety and Efficacy of Gadobutrol for Contrast-enhanced Magnetic Resonance Imaging of the Central Nervous System: Results from a Multicenter, Double-blind, Randomized, Comparator Study. Magn Reson Insights. 2015 Apr 7;8:1-10. doi: 10.4137/MRI.S19794. eCollection 2015. [Article]
- FDA Approved Drug Products: Prohance (gadoteridol) injection for intravenous administration [Link]
- FDA Approved Drug Products: PROHANCE (gadoteridol injection) single dose, for intravenous use (Jan 2024) [Link]
- FDA Approves Bracco Diagnostics Inc.'s ProHance® (Gadoteridol) Injection, 279.3 mg/mL, for Pediatric Patients Younger than Two Years [Link]
- External Links
- Human Metabolome Database
- HMDB0014735
- KEGG Drug
- D01137
- PubChem Compound
- 60714
- PubChem Substance
- 46505738
- ChemSpider
- 54719
- 25483
- ChEBI
- 31643
- ChEMBL
- CHEMBL1200593
- PharmGKB
- PA164746463
- Wikipedia
- Gadoteridol
- FDA label
- Download (195 KB)
- MSDS
- Download (60.6 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Diagnostic Brain Disorders 1 4 Completed Diagnostic Coronary Artery Disease (CAD) / Type 1 Diabetes Mellitus 1 4 Recruiting Other Cognitive Functioning / Contrast Medium / Motor Function 1 3 Completed Diagnostic Brain Metastases 1 3 Completed Diagnostic Central Nervous System Disorder / Imaging procedure 1
Pharmacoeconomics
- Manufacturers
- Bracco diagnostics inc
- Packagers
- Bracco Diagnostics Inc.
- Nycomed Inc.
- Dosage Forms
Form Route Strength Injection, solution Intravenous 279.3 mg/1mL Injection, solution Intravenous 279.3 MG/ML Solution Intravenous 279.3 mg Injection, solution Parenteral Solution Intravenous 279.3 mg / mL Liquid Intravenous 279.3 mg / mL - Prices
Unit description Cost Unit Prohance 279.3 mg/ml vial 6.81USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5474756 No 1995-12-12 2012-12-12 US CA1341176 No 2001-01-30 2018-01-30 Canada US5846519 No 1998-12-08 2015-12-08 US
Properties
- State
- Liquid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 11.2 mg/mL ALOGPS logP 0.36 ALOGPS logP -6.8 Chemaxon logS -1.8 ALOGPS pKa (Strongest Acidic) 1.46 Chemaxon pKa (Strongest Basic) 8.3 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 11 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 153.58 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 133.55 m3·mol-1 Chemaxon Polarizability 39.38 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
Property Value Probability Human Intestinal Absorption - 0.8097 Blood Brain Barrier + 0.6442 Caco-2 permeable - 0.5567 P-glycoprotein substrate Substrate 0.7825 P-glycoprotein inhibitor I Non-inhibitor 0.8295 P-glycoprotein inhibitor II Non-inhibitor 0.8408 Renal organic cation transporter Non-inhibitor 0.8026 CYP450 2C9 substrate Non-substrate 0.8605 CYP450 2D6 substrate Non-substrate 0.769 CYP450 3A4 substrate Non-substrate 0.6437 CYP450 1A2 substrate Non-inhibitor 0.8814 CYP450 2C9 inhibitor Non-inhibitor 0.8843 CYP450 2D6 inhibitor Non-inhibitor 0.8737 CYP450 2C19 inhibitor Non-inhibitor 0.81 CYP450 3A4 inhibitor Non-inhibitor 0.908 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9838 Ames test Non AMES toxic 0.7586 Carcinogenicity Non-carcinogens 0.9134 Biodegradation Not ready biodegradable 0.6054 Rat acute toxicity 2.1688 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6113 hERG inhibition (predictor II) Non-inhibitor 0.8966
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-05mt-3009000000-8c8257add253983cc0f1 - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 192.4242271 predictedDarkChem Lite v0.1.0 [M+H]+ 191.0985271 predictedDarkChem Lite v0.1.0 [M+Na]+ 191.2400271 predictedDarkChem Lite v0.1.0
Drug created at June 13, 2005 13:24 / Updated at April 16, 2024 12:20