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Identification
NameGadobenate Dimeglumine
Accession NumberDB00743  (APRD00989)
TypeSmall Molecule
GroupsApproved
Description

Gadobenate Dimeglumine is an MRI contrast agent used primarily for MR imaging of the liver. It can also be used for visualizing the CNS and heart. In contrast to conventional extracellular fluid contrast agents, gadobenate dimeglumine is characterized by a weak and transient binding capacity to serum proteins. This binding leads to an increased relaxivity of gadobenate dimeglumine and, consequently, to a considerably increased signal intensity over that of other agents.

Structure
Thumb
Synonyms
SynonymLanguageCode
Acide gadobeniqueFrenchINN
Acido gadobenicoSpanishINN
Acidum gadobenicum LatinINN
Gadobenate dimeglumineNot AvailableNot Available
Gadobenic acidNot AvailableBAN
GadobensäureGermanINN
MultihanceNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
MultihanceBracco
Multihance MultipackBracco
Brand mixturesNot Available
Categories
CAS number113662-23-0
WeightAverage: 1058.15
Monoisotopic: 1058.317829604
Chemical FormulaC36H62GdN5O21
InChI KeyOCDAWJYGVOLXGZ-VPVMAENOSA-K
InChI
InChI=1S/C22H31N3O11.2C7H17NO5.Gd/c26-18(27)10-23(6-7-24(11-19(28)29)12-20(30)31)8-9-25(13-21(32)33)17(22(34)35)15-36-14-16-4-2-1-3-5-16;2*1-8-2-4(10)6(12)7(13)5(11)3-9;/h1-5,17H,6-15H2,(H,26,27)(H,28,29)(H,30,31)(H,32,33)(H,34,35);2*4-13H,2-3H2,1H3;/q;;;+3/p-3/t;2*4-,5+,6+,7+;/m.00./s1
IUPAC Name
gadolinium(3+) ion bis((2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-pentol) 8-(carboxylatomethyl)-5,11-bis(carboxymethyl)-1-phenyl-2-oxa-5,8,11-triazatridecane-4,13-dioate
SMILES
[Gd+3].CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC(=O)CN(CCN(CCN(CC(O)=O)C(COCC1=CC=CC=C1)C([O-])=O)CC([O-])=O)CC([O-])=O
Mass SpecNot Available
Taxonomy
KingdomNot Available
SuperclassNot Available
ClassNot Available
SubclassNot Available
Direct parentNot Available
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationGadobenate Dimeglumine is an MRI contrast agent used primarily for MR imaging of the liver. It can also be used for MRI of the heart, as well as and central nervous system in adults to visualize lesions with abnormal brain vascularity or abnormalities in the blood brain barrier, the brain, spine, or other associated tissues.
PharmacodynamicsGadobenate dimeglumine shares the pharmacokinetic properties of the ECF contrast agent gadopentetate dimeglumine; however, gadobenate differs in that is also selectively taken-up by hepatocytes and excreted via the bile (up to 5% of dose). The elimination half-life of gadobenate dimeglumine is approximately 1 hour. It is not metabolized.
Mechanism of actionBased 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 2 different relaxation processes, the T1 (spin-lattice or longitudinal relaxation time) and the T2 (spin-spin or transverse relaxation time). In magnetic resonance imaging (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 the T2. When placed in a magnetic field, Gadobenate Dimeglumine shortens both the T1 and the T2 relaxation times in tissues where it accumulates. At clinical doses, Gadobenate Dimeglumine primarily affects the T1 relaxation time, thus producing an increase in signal intensity. Gadobenate Dimeglumine 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).
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingPlasma protein binding is low, weak, and transient.
Metabolism

Not metabolized.

Route of eliminationGadobenate ion is eliminated predominately via the kidneys, with 78% to 96% of an administered dose recovered in the urine.
Half life1 hour
Clearance
  • 0.093 +/- 0.010 L/hr/kg [healthy male subjects receiving 3 single-dose IV administration with doses from 0.005-0.4 mmol/kg]
ToxicityGadolinium-based radiocontrast agents like gadobenate dimeglumine are cytotoxic to renal cells. The toxic effects include apoptosis, cellular energy failure, disruption of calcium homeostasis, and disturbance of tubular cell polarity, and are thought to be linked to oxidative stress.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.9749
Blood Brain Barrier - 0.9391
Caco-2 permeable - 0.691
P-glycoprotein substrate Substrate 0.8261
P-glycoprotein inhibitor I Non-inhibitor 0.7702
P-glycoprotein inhibitor II Non-inhibitor 0.7288
Renal organic cation transporter Non-inhibitor 0.8635
CYP450 2C9 substrate Non-substrate 0.8598
CYP450 2D6 substrate Non-substrate 0.8006
CYP450 3A4 substrate Non-substrate 0.6356
CYP450 1A2 substrate Non-inhibitor 0.8637
CYP450 2C9 substrate Non-inhibitor 0.8597
CYP450 2D6 substrate Non-inhibitor 0.8675
CYP450 2C19 substrate Non-inhibitor 0.8851
CYP450 3A4 substrate Non-inhibitor 0.9349
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9905
Ames test Non AMES toxic 0.8062
Carcinogenicity Non-carcinogens 0.9179
Biodegradation Not ready biodegradable 0.8088
Rat acute toxicity 2.3557 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8499
hERG inhibition (predictor II) Non-inhibitor 0.6371
Pharmacoeconomics
Manufacturers
  • Bracco diagnostics inc
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
Prices
Unit descriptionCostUnit
Multihance 529 mg/ml vial6.87USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States49162461995-04-102012-04-10
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
logP-4.1ChemAxon
pKa (Strongest Acidic)0.085ChemAxon
pKa (Strongest Basic)9.58ChemAxon
Physiological Charge-4ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area213.94 Å2ChemAxon
Rotatable Bond Count32ChemAxon
Refractivity154.36 m3·mol-1ChemAxon
Polarizability48.51 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Pier Lucio Anelli, Pierfrancesco Morisini, Silvia Ceragioli, Fulvio Uggeri, Luciano Lattuada, Roberta Fretta, Aurelia Ferrigato, “Process for the Preparation of Gadobenate Dimeglumine Complex in a Solid Form.” U.S. Patent US20120232151, issued September 13, 2012.

US20120232151
General Reference
  1. de Haen C, Cabrini M, Akhnana L, Ratti D, Calabi L, Gozzini L: Gadobenate dimeglumine 0.5 M solution for injection (MultiHance) pharmaceutical formulation and physicochemical properties of a new magnetic resonance imaging contrast medium. J Comput Assist Tomogr. 1999 Nov;23 Suppl 1:S161-8. Pubmed
  2. Morana G, Salviato E, Guarise A: Contrast agents for hepatic MRI. Cancer Imaging. 2007 Oct 1;7 Spec No A:S24-7. Pubmed
  3. Vogl TJ, Pegios W, McMahon C, Balzer J, Waitzinger J, Pirovano G, Lissner J: Gadobenate dimeglumine—a new contrast agent for MR imaging: preliminary evaluation in healthy volunteers. AJR Am J Roentgenol. 1992 Apr;158(4):887-92. Pubmed
  4. Kirchin MA, Pirovano GP, Spinazzi A: Gadobenate dimeglumine (Gd-BOPTA). An overview. Invest Radiol. 1998 Nov;33(11):798-809. Pubmed
  5. Clement O, Siauve N, Cuenod CA, Vuillemin-Bodaghi V, Leconte I, Frija G: Mechanisms of action of liver contrast agents: impact for clinical use. J Comput Assist Tomogr. 1999 Nov;23 Suppl 1:S45-52. Pubmed
External Links
ResourceLink
PubChem Compound6918204
PubChem Substance46506805
ChemSpider170831
Therapeutic Targets DatabaseDAP001225
PharmGKBPA164745426
Drug Product Database2248302
ATC CodesV08CA08
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelshow(247 KB)
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Port M, Corot C, Violas X, Robert P, Raynal I, Gagneur G: How to compare the efficiency of albumin-bound and nonalbumin-bound contrast agents in vivo: the concept of dynamic relaxivity. Invest Radiol. 2005 Sep;40(9):565-73. Pubmed
  2. Wendland MF, Saeed M, Lauerma K, Derugin N, Mintorovitch J, Cavagna FM, Higgins CB: Alterations in T1 of normal and reperfused infarcted myocardium after Gd-BOPTA versus GD-DTPA on inversion recovery EPI. Magn Reson Med. 1997 Mar;37(3):448-56. Pubmed
  3. Cavagna FM, Maggioni F, Castelli PM, Dapra M, Imperatori LG, Lorusso V, Jenkins BG: Gadolinium chelates with weak binding to serum proteins. A new class of high-efficiency, general purpose contrast agents for magnetic resonance imaging. Invest Radiol. 1997 Dec;32(12):780-96. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on January 06, 2014 13:44