Gadoteridol

Identification

Name
Gadoteridol
Accession Number
DB00597  (APRD00992)
Type
Small Molecule
Groups
Approved, Investigational
Description

Gadoteridol 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 cause a disruption of the normal blood brain barrier. Gadoteridol can also be used for whole body contrast enhanced MRI including the head, neck, liver, breast, musculoskeletal system and soft tissue pathologies. n MRI, visualization of normal and pathological brain tissue depends in part on variations in the radiofrequency signal intensity that occur with changes in proton density, alteration of the T1, and variation in T2. When placed in a magnetic field, gadoteridol shortens the T1 relaxation time in tissues where it accumulates. Abnormal vascularity or disruption of the blood-brain barrier allows accumulation of gadoteridol in lesions such as neoplasms, abscesses, and subacute infarcts.

Structure
Thumb
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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ProHanceInjection, solution279.3 mg/1mLIntravenousBracco Diagnostics, Inc2003-10-09Not applicableUs
ProHanceInjection, solution279.3 mg/1mLIntravenousBIPSO GmbH1992-11-16Not applicableUs
Prohance - Liq IV 279.3mg/mlSolution279.3 mgIntravenousBracco Imaging S.P.A.1998-09-08Not applicableCanada
Prohance Liq IV 279.3mg/mlLiquid279.3 mgIntravenousSquibb Diagnostics, Division Of Bristol Myers Squibb Canada Inc.1993-12-311998-07-30Canada
Categories
UNII
0199MV609F
CAS number
120066-54-8
Weight
Average: 558.68
Monoisotopic: 559.127724835
Chemical Formula
C17H29GdN4O7
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+) ion 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

Pharmacology

Indication

Gadoteridol is an MRI contrast agent used for 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 cause a disruption of the normal blood brain barrier. Gadoteridol can also be used for whole body contrast enhanced MRI including the head, neck, liver, breast, musculoskeletal system and soft tissue pathologies.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Based on the behavior of protons when placed in a strong magnetic field, which is interpreted and transformed into images by magnetic resonance (MR) instruments. Paramagnetic agents have unpaired electrons that generate a magnetic field about 700 times larger than the proton's field, thus disturbing the proton's local magnetic field. When the local magnetic field around a proton is disturbed its relaxation process is altered. MR images are based on proton density and proton relaxation dynamics. MR instruments can record two different relaxation processes, the T1 (spin-lattice or longitudinal relaxation time) and T2 (spin-spin or transverse relaxation time). In MRI, visualization of normal and pathological brain tissue depends in part on variations in the radiofrequency signal intensity that occur with changes in proton density, alteration of the T1, and variation in T2. When placed in a magnetic field, gadoteridol shortens the T1 relaxation time in tissues where it accumulates. Gadoteridol does not cross the intact blood-brain barrier; therefore, it does not accumulate in normal brain tissue or in central nervous system (CNS) lesions that have not caused an abnormal blood-brain barrier (e.g., cysts, mature post-operative scars). Abnormal vascularity or disruption of the blood-brain barrier allows accumulation of gadoteridol in lesions such as neoplasms, abscesses, and subacute infarcts.

Absorption
Not Available
Volume of distribution
  • 204 ± 58 mL/kg
Protein binding
Not Available
Metabolism
Not Available
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.

Half life

Distribution 12 minutes (mean), elimination 100 minutes (mean).

Clearance
  • 1.50+/- 0.35 mL/ min/kg
  • renal cl=1.41 +/- 0.33 mL/ min/kg
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetaminophenAcetaminophen may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
AlprazolamAlprazolam may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
AmilorideAmiloride may increase the excretion rate of Gadoteridol which could result in a lower serum level and potentially a reduction in efficacy.
AmitriptylineGadoteridol may decrease the excretion rate of Amitriptyline which could result in a higher serum level.
AmlodipineAmlodipine may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
AmoxicillinGadoteridol may decrease the excretion rate of Amoxicillin which could result in a higher serum level.
AmphetamineAmphetamine may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
AmpicillinAmpicillin may decrease the excretion rate of Gadoteridol which could result in a higher serum level.
AuranofinGadoteridol may decrease the excretion rate of Auranofin which could result in a higher serum level.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014735
KEGG Drug
D01137
PubChem Compound
60714
PubChem Substance
46505738
ChemSpider
54719
ChEBI
31643
ChEMBL
CHEMBL1200593
PharmGKB
PA164746463
Wikipedia
Gadoteridol
ATC Codes
V08CA04 — Gadoteridol
AHFS Codes
  • 36:89.00* — Other Diagnostics
FDA label
Download (195 KB)
MSDS
Download (60.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedDiagnosticCentral Nervous System Diseases / Diagnostic Imaging1
3CompletedDiagnosticMetastatic Brain Tumors1
4CompletedDiagnosticBrain Diseases1
4CompletedDiagnosticCoronary Artery Disease / Diabetes, Diabetes Mellitus Type 11
Not AvailableNot Yet RecruitingNot AvailableDisseminated Sclerosis1
Not AvailableRecruitingBasic ScienceDisseminated Sclerosis1
Not AvailableRecruitingDiagnosticAdult Brain Glioblastoma1

Pharmacoeconomics

Manufacturers
  • Bracco diagnostics inc
Packagers
  • Bracco Diagnostics Inc.
  • Nycomed Inc.
Dosage forms
FormRouteStrength
Injection, solutionIntravenous279.3 mg/1mL
SolutionIntravenous279.3 mg
LiquidIntravenous279.3 mg
Prices
Unit descriptionCostUnit
Prohance 279.3 mg/ml vial6.81USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5474756No1992-12-122012-12-12Us
CA1341176No2001-01-302018-01-30Canada
US5846519No1995-12-082015-12-08Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility11.2 mg/mLALOGPS
logP0.36ALOGPS
logP-7.5ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)0.76ChemAxon
pKa (Strongest Basic)10ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area153.58 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity133.55 m3·mol-1ChemAxon
Polarizability39.42 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8097
Blood Brain Barrier+0.6442
Caco-2 permeable-0.5567
P-glycoprotein substrateSubstrate0.7825
P-glycoprotein inhibitor INon-inhibitor0.8295
P-glycoprotein inhibitor IINon-inhibitor0.8408
Renal organic cation transporterNon-inhibitor0.8026
CYP450 2C9 substrateNon-substrate0.8605
CYP450 2D6 substrateNon-substrate0.769
CYP450 3A4 substrateNon-substrate0.6437
CYP450 1A2 substrateNon-inhibitor0.8814
CYP450 2C9 inhibitorNon-inhibitor0.8843
CYP450 2D6 inhibitorNon-inhibitor0.8737
CYP450 2C19 inhibitorNon-inhibitor0.81
CYP450 3A4 inhibitorNon-inhibitor0.908
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9838
Ames testNon AMES toxic0.7586
CarcinogenicityNon-carcinogens0.9134
BiodegradationNot ready biodegradable0.6054
Rat acute toxicity2.1688 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6113
hERG inhibition (predictor II)Non-inhibitor0.8966
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Alpha-amino acid / Tricarboxylic acid or derivatives / 1,2-aminoalcohol / Carboxylic acid salt / Secondary alcohol / Tertiary amine / Tertiary aliphatic amine / Amino acid / Carboxylic acid / Organoheterocyclic compound
show 14 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
gadolinium coordination entity (CHEBI:31643)

Drug created on June 13, 2005 07:24 / Updated on September 21, 2018 00:03