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Identification
NameGadofosveset trisodium
Accession NumberDB06705
TypeSmall Molecule
GroupsApproved
Description

Gadofosveset trisodium is an intravenous contrast agent used with magnetic resonance angiography(MRA), which is a non-invasive way of imaging blood vessels. The agent allows for the vascular system to be imaged more clearly by the MRA. In this way, gadofosveset trisodium is used to help diagnose certain disorders of the heart and blood vessels.

Structure
Thumb
Synonyms
SynonymLanguageCode
AblavarNot AvailableNot Available
GadofosvesetNot AvailableNot Available
MS-325 Not AvailableNot Available
VasovistNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ablavarinjection, solution244 mg/mLintravenousLantheus Medical Imaging, Inc.2008-12-12Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
VasovistBayer
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number193901-90-5
WeightAverage: 975.87
Monoisotopic: 976.113113695
Chemical FormulaC33H40GdN3Na3O15P
InChI KeyPIZALBORPSCYJU-UHFFFAOYSA-H
InChI
InChI=1S/C33H44N3O14P.Gd.3Na.H2O/c37-28(38)18-34(15-16-35(19-29(39)40)20-30(41)42)17-26(36(21-31(43)44)22-32(45)46)23-49-51(47,48)50-27-11-13-33(14-12-27,24-7-3-1-4-8-24)25-9-5-2-6-10-25;;;;;/h1-10,26-27H,11-23H2,(H,37,38)(H,39,40)(H,41,42)(H,43,44)(H,45,46)(H,47,48);;;;;1H2/q;+3;3*+1;/p-6
IUPAC Name
gadolinium(3+) ion trisodium 2-{[1-({2-[bis(carboxylatomethyl)amino]ethyl}(carboxylatomethyl)amino)-3-[(4,4-diphenylcyclohexyl phosphonato)oxy]propan-2-yl](carboxylatomethyl)amino}acetate hydrate
SMILES
O.[Na+].[Na+].[Na+].[Gd+3].[O-]C(=O)CN(CCN(CC([O-])=O)CC([O-])=O)CC(COP([O-])(=O)OC1CCC(CC1)(C1=CC=CC=C1)C1=CC=CC=C1)N(CC([O-])=O)CC([O-])=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pentacarboxylic acids and derivatives. These are carboxylic acids containing exactly five carboxyl groups.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassPentacarboxylic acids and derivatives
Direct ParentPentacarboxylic acids and derivatives
Alternative Parents
Substituents
  • Pentacarboxylic acid or derivatives
  • Diphenylmethane
  • Alpha-amino acid or derivatives
  • Alpha-amino acid
  • Phosphoethanolamine
  • Dialkyl phosphate
  • Benzenoid
  • Alkyl phosphate
  • Phosphoric acid ester
  • Organic phosphoric acid derivative
  • Organic phosphate
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid salt
  • Carboxylic acid
  • Hydrocarbon derivative
  • Organic alkali metal salt
  • Organic sodium salt
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Organic zwitterion
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationGadofosveset trisodium is indicated for use as a contrast agent in magnetic resonance angiography (MRA) to evaluate aortoiliac occlusive disease (AIOD) in adults with known or suspected peripheral vascular disease.
PharmacodynamicsGadofosveset causes signal enhancement by shortening the T1 of water molecules that interact with it. The contrast agent complex's rotation rate is the primary factor determining the magnitude of relaxation enhancement. This relaxation enhancement increase only occurs when bound to human serum albumin.
Mechanism of actionGadofosveset binds reversibly to endogenous serum albumin resulting in longer vascular residence time than non-protein binding contrast agents. The binding to serum albumin also increases the magnetic resonance relaxivity of gadofosveset and decreases the relaxation time (Tl) of water protons resulting in an increase in signal intensity (brightness) of blood.
AbsorptionNot Available
Volume of distribution

48 ± 16 mL/kg

Protein binding80-90%
Metabolism

Gadofosveset does not undergo measurable metabolism.

Route of eliminationGadofosveset is eliminated primarily in the urine with approximately 83.5% of an injected dose excreted in the urine over 14 days. Ninety-four percent (94%) of urinary excretion occurs in the first 72 hours. A small portion of gadofosveset dose is recovered in feces (approximately 4.7%).
Half life18.5 hours
Clearance

6.57 ± 0.97 mL/h/kg following the administration of 0.03 mmol/kg.

ToxicityGadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with acute or chronic severe renal insufficiency (glomerular filtration rate < 30 mL/min/1.73m²).
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8572
Blood Brain Barrier+0.6355
Caco-2 permeable-0.5948
P-glycoprotein substrateSubstrate0.6107
P-glycoprotein inhibitor IInhibitor0.6422
P-glycoprotein inhibitor IINon-inhibitor0.6901
Renal organic cation transporterNon-inhibitor0.6739
CYP450 2C9 substrateNon-substrate0.7903
CYP450 2D6 substrateNon-substrate0.8158
CYP450 3A4 substrateNon-substrate0.5501
CYP450 1A2 substrateNon-inhibitor0.7768
CYP450 2C9 substrateNon-inhibitor0.7121
CYP450 2D6 substrateNon-inhibitor0.8278
CYP450 2C19 substrateNon-inhibitor0.6916
CYP450 3A4 substrateNon-inhibitor0.7875
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8798
Ames testNon AMES toxic0.6081
CarcinogenicityNon-carcinogens0.7542
BiodegradationNot ready biodegradable0.9604
Rat acute toxicity2.6392 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5557
hERG inhibition (predictor II)Non-inhibitor0.5302
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, solutionintravenous244 mg/mL
PricesNot Available
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada22111002007-03-202016-01-16
Canada23044612008-10-142018-08-17
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
logP-1.2ChemAxon
pKa (Strongest Acidic)0.78ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge-5ChemAxon
Hydrogen Acceptor Count15ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area268.96 Å2ChemAxon
Rotatable Bond Count23ChemAxon
Refractivity241.55 m3·mol-1ChemAxon
Polarizability69.9 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Raman FS, Nacif MS, Cater G, Gai N, Jones J, Li D, Sibley CT, Liu S, Bluemke DA: 3.0-T whole-heart coronary magnetic resonance angiography: comparison of gadobenate dimeglumine and gadofosveset trisodium. Int J Cardiovasc Imaging. 2013 Mar 21. Pubmed
  2. Hrdina L, Kocher M, Herman M, Cerna M, Kozak J, Tudos Z, Mahathmakanthi S, Langova K: Comparison of the quality of lower limb magnetic resonance angiographies performed with different paramagnetic contrast agents in relation to body mass index and ejection fraction. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012 Jun;156(2):164-70. doi: 10.5507/bp.2011.058. Pubmed
  3. Thouet T, Schnackenburg B, Kokocinski T, Fleck E, Nagel E, Kelle S: Visualization of chronic myocardial infarction using the intravascular contrast agent MS-325 (gadofosveset) in patients. ScientificWorldJournal. 2012;2012:236401. doi: 10.1100/2012/236401. Epub 2012 Mar 12. Pubmed
  4. Milot L, Haider M, Foster L, McGregor C, Law C: Gadofosveset trisodium in the investigation of focal liver lesions in noncirrhotic liver: Early experience. J Magn Reson Imaging. 2012 Sep;36(3):738-42. doi: 10.1002/jmri.23650. Epub 2012 Apr 5. Pubmed
  5. Caravan P: Protein-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agents: design and mechanism of action. Acc Chem Res. 2009 Jul 21;42(7):851-62. doi: 10.1021/ar800220p. Pubmed
External Links
ATC CodesV08CA11
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (148 KB)
MSDSDownload (66.5 KB)
Interactions
Drug Interactions
Drug
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
WarfarinIn a clinical trial of 10 patients receiving a stable dose of warfarin, a single dose of ABLAVAR (0.05 mmol/kg) did not alter the anticoagulant activity of warfarin as measured by the International Normalized Ratio (INR).
Food InteractionsNot Available

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Meaney JF, Goyen M: Recent advances in contrast-enhanced magnetic resonance angiography. Eur Radiol. 2007 Mar;17 Suppl 2:B2-6. Pubmed
  2. Caravan P: Protein-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agents: design and mechanism of action. Acc Chem Res. 2009 Jul 21;42(7):851-62. Pubmed
  3. Caravan P, Parigi G, Chasse JM, Cloutier NJ, Ellison JJ, Lauffer RB, Luchinat C, McDermid SA, Spiller M, McMurry TJ: Albumin binding, relaxivity, and water exchange kinetics of the diastereoisomers of MS-325, a gadolinium(III)-based magnetic resonance angiography contrast agent. Inorg Chem. 2007 Aug 6;46(16):6632-9. Epub 2007 Jul 11. Pubmed
  4. Henness S, Keating GM: Gadofosveset. Drugs. 2006;66(6):851-7. Pubmed

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Drug created on May 15, 2010 18:37 / Updated on September 16, 2013 18:04