NAV

Gadobenic acid

Identification

Summary

Gadobenic acidis a gadolinium compound used as a contrast agent in MRIs.

Brand Names
Multihance
Generic Name
Gadobenic acid
DrugBank Accession Number
DB00743
Background

Gadobenic acid (in the form of 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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
MOL SDF PDB SMILES InChI
Similar Structures
Weight
Average: 667.73
Monoisotopic: 668.09649
Chemical Formula
C22H28GdN3O11
Synonyms
  • Acide gadobenique
  • Acido gadobenico
  • Acidum gadobenicum
  • Gadobenate
  • Gadobenic acid
  • Gadobensäure
External IDs
  • B 19036
  • B 19036/7

Pharmacology

Indication

Gadobenate dimeglumine is indicated for use in magnetic resonance imaging (MRI) of the central nervous system in adult and pediatric patients in order to visualize lesions with abnormal blood-brain barrier or abnormal vascularity of the brain, spine, and associated tissues.7它也用于磁共振表示angiography (MRA) to evaluate adults with known or suspected renal or aorto-ilio-femoral occlusive vascular disease.7

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Associated Conditions
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Pharmacodynamics

Gadobenate 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 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 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).

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Plasma protein binding is low, weak, and transient.

Metabolism

Not metabolized.

Route of elimination

Gadobenate ion is eliminated predominately via the kidneys, with 78% to 96% of an administered dose recovered in the urine.

Half-life

1 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]
Adverse Effects
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Toxicity

Gadolinium-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.

Pathways
Not Available
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Not Available

Interactions

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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 Gadobenic acid may decrease the excretion rate of Abacavir which could result in a higher serum level.
Aceclofenac Aceclofenac可能减少迦得的排泄率obenic acid which could result in a higher serum level.
Acemetacin Acemetacin may decrease the excretion rate of Gadobenic acid which could result in a higher serum level.
18beplay下载 Acetaminophen may decrease the excretion rate of Gadobenic acid which could result in a higher serum level.
Acetazolamide Acetazolamide may increase the excretion rate of Gadobenic 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 Gadobenic acid which could result in a higher serum level.
Aclidinium Gadobenic acid may decrease the excretion rate of Aclidinium which could result in a higher serum level.
Acrivastine The risk or severity of QTc prolongation can be increased when Acrivastine is combined with Gadobenic acid.
Acyclovir Acyclovir may decrease the excretion rate of Gadobenic acid which could result in a higher serum level.
Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Gadobenic 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
Gadobenate dimeglumine 3Q6PPC19PO 127000-20-8 OCDAWJYGVOLXGZ-VPVMAENOSA-K
Active Moieties
Name Kind UNII CAS InChI Key
Gadolinium cation (3+) ionic AZV954TZ9N 22541-19-1 RJOJUSXNYCILHH-UHFFFAOYSA-N
International/Other Brands
Multihance Multipack (Bracco)
Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image
MultiHance Injection, solution 529 mg/1mL Intravenous Bracco Diagnostics Inc 2004-11-23 Not applicable US flag
MultiHance Solution 529 mg / mL Intravenous Bracco Imaging S.P.A. 2004-10-28 Not applicable Canada flag
MultiHance Injection, solution 529 mg/1mL Intravenous Bracco Diagnostics Inc 2004-11-23 Not applicable US flag
Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image
MULTIHANCE INJECTION 10 ML Gadobenate dimeglumine(529 mg/ml)+Gadobenate dimeglumine(529 mg/ml) Injection Intravenous DCH御夫座新加坡 2004-01-30 Not applicable
MULTIHANCE INJECTION 10 ML Gadobenate dimeglumine(529 mg/ml)+Gadobenate dimeglumine(529 mg/ml) Injection Intravenous DCH御夫座新加坡 2004-01-30 Not applicable

Categories

ATC Codes
V08CA08 — Gadobenic acid
Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
15G12L5X8K
CAS number
113662-23-0
InChI Key
MXZROTBGJUUXID-UHFFFAOYSA-K
InChI
InChI=1S/C22H31N3O11.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;/h1-5,17H,6-15H2,(H,26,27)(H,28,29)(H,30,31)(H,32,33)(H,34,35);/q;+3/p-3
IUPAC Name
gadolinium(3+) ion 4-carboxy-8,11-bis(carboxylatomethyl)-5-(carboxymethyl)-1-phenyl-2-oxa-5,8,11-triazatridecan-13-oate
SMILES
[Gd+3].OC(=O)CN(CCN(CCN(CC([O-])=O)CC([O-])=O)CC([O-])=O)C(COCC1=CC=CC=C1)C(O)=O

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 References
  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. [Article]
  2. Morana G, Salviato E, Guarise A: Contrast agents for hepatic MRI. Cancer Imaging. 2007 Oct 1;7 Spec No A:S24-7. [Article]
  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. [Article]
  4. Kirchin MA, Pirovano GP, Spinazzi A: Gadobenate dimeglumine (Gd-BOPTA). An overview. Invest Radiol. 1998 Nov;33(11):798-809. [Article]
  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. [Article]
  6. Sweetman, Sean C. (2009). Contrast Media. In Martindale : The Complete Drug Reference, 36th Edition 2 Volume Set (36th ed., pp. 1478). Pharmaceutical Press. [ISBN:978-0-85369-840-1]
  7. FDA Approved Drug Products: MultiHance (gadobenate dimeglumine) for injection [Link]
KEGG Drug
D08018
PubChem Compound
131704172
PubChem Substance
46506805
ChemSpider
94843
RxNav
692620
ChEMBL
CHEMBL1200571
Therapeutic Targets Database
DAP001225
PharmGKB
PA164745426
Wikipedia
Gadobenic_acid
FDA label
Download (247 KB)

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
4 Completed Not Available Brain Pathology 1
4 Completed Diagnostic Brain Disorders 1
4 Completed Diagnostic Brain Lesions 1
4 Completed Diagnostic Brain Neoplasm 1
4 Recruiting Diagnostic Colorectal Cancer/Metastatic Cancer to Liver/Oligometastatic Disease 1
4 Recruiting Other Cognitive Functioning/Contrast Medium/Motor Function 1
3 Completed Diagnostic Breast Cancer 1
3 Completed Diagnostic Carotid, Aortic, Renal or Peripheral Artery Disease 1
3 Completed Diagnostic Peripheral Vascular Disease Patient 1
3 Completed Diagnostic Steno-Occlusive Disease 1

Pharmacoeconomics

Manufacturers
  • Bracco diagnostics inc
Packagers
  • Bracco Diagnostics Inc.
  • Nycomed Inc.
  • Patheon Inc.
Dosage Forms
Form Route Strength
Injection Intravenous 0.529 g/ml
Injection, solution Intravenous
Injection, solution Intravenous 529 mg/1mL
Solution Intravenous 334 mg/1ml
Solution Intravenous 529 mg / mL
Injection, solution Parenteral 529 mg/ml
Injection, solution Parenteral
Injection Intravenous 529 mg/ml
Injection Intravenous 529 mg/ml
Solution Intravenous 10 ml
Solution Intravenous 15 ml
Solution Intravenous 20 ml
Solution Intravenous
Prices
Unit description Cost Unit
Multihance 529 mg/ml vial 6.87USD 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
US4916246 No 1990-04-10 2012-04-10 US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Property Value Source
Water Solubility 0.768 mg/mL ALOGPS
logP 0.92 ALOGPS
logP -4.1 Chemaxon
logS -3 ALOGPS
pKa (Strongest Acidic) 0.085 Chemaxon
pKa (Strongest Basic) 9.58 Chemaxon
Physiological Charge -3 Chemaxon
Hydrogen Acceptor Count 14 Chemaxon
Hydrogen Donor Count 2 Chemaxon
Polar Surface Area 213.94 Å2 Chemaxon
Rotatable Bond Count 20 Chemaxon
Refractivity 154.36 m3·mol-1 Chemaxon
Polarizability 48.32 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 - 0.9749
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 inhibitor Non-inhibitor 0.8597
CYP450 2D6 inhibitor Non-inhibitor 0.8675
CYP450 2C19 inhibitor Non-inhibitor 0.8851
CYP450 3A4 inhibitor 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
ADMET data is predicted usingadmetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Carriers

Details 1.Serum albumin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
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. [Article]
  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. [Article]
  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. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Drug created at June 13, 2005 13:24 / Updated at April 25, 2023 04:47