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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
Gadofosveset
External Identifiers
  • MS-325
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ablavarinjection, solution244 mg/mLintravenousLantheus Medical Imaging, Inc.2008-12-12Not applicableUs
Ablavarsolution244 mgintravenousLantheus Mi Canada Inc2010-10-122016-03-07Canada
Vasovistsolution244 mgintravenousBayer Inc2007-08-202009-08-06Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Gadofosveset trisodium monohydrate
211570-55-7
Thumb
  • InChI Key: PIZALBORPSCYJU-QSQMUHTISA-H
  • Monoisotopic Mass: 976.11312
  • Average Mass: 975.88
DBSALT001858
Categories
UNII9430ZR8ZAN
CAS number193901-90-5
WeightAverage: 957.87
Monoisotopic: 958.10256
Chemical FormulaC33H38GdN3Na3O14P
InChI KeyXGOSYNSWSRUASG-UHFFFAOYSA-H
InChI
InChI=1S/C33H44N3O14P.Gd.3Na/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);;;;/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
SMILES
[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
  • Alpha-amino acid or derivatives
  • Phosphoethanolamine
  • Dialkyl phosphate
  • Monocyclic benzene moiety
  • Organic phosphoric acid derivative
  • Phosphoric acid ester
  • Benzenoid
  • Alkyl phosphate
  • Amino acid or derivatives
  • Carboxylic acid salt
  • Amino acid
  • Tertiary amine
  • Tertiary aliphatic amine
  • Organic alkali metal salt
  • Carboxylic acid
  • Organooxygen compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Amine
  • Organic oxygen compound
  • Carbonyl group
  • Organic oxide
  • Organic sodium salt
  • Organic salt
  • Organic nitrogen compound
  • 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.
Related Articles
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 inhibitorNon-inhibitor0.7121
CYP450 2D6 inhibitorNon-inhibitor0.8278
CYP450 2C19 inhibitorNon-inhibitor0.6916
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, solutionintravenous244 mg/mL
Solutionintravenous244 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2211100 No2007-03-202016-01-16Canada
CA2304461 No2008-10-142018-08-17Canada
US6676929 No2000-05-042020-05-04Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.169 mg/mLALOGPS
logP3.84ALOGPS
logP-1.2ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)0.78ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge-4ChemAxon
Hydrogen Acceptor Count15ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area268.96 Å2ChemAxon
Rotatable Bond Count23ChemAxon
Refractivity241.55 m3·mol-1ChemAxon
Polarizability69.28 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 References
  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 Jun;29(5):1085-94. doi: 10.1007/s10554-013-0192-z. Epub 2013 Mar 21. [PubMed:23515949 ]
  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:22660207 ]
  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:22536125 ]
  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:22488745 ]
  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:19222207 ]
External Links
ATC CodesV08CA11
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (148 KB)
MSDSDownload (66.5 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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 colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. Meaney JF, Goyen M: Recent advances in contrast-enhanced magnetic resonance angiography. Eur Radiol. 2007 Mar;17 Suppl 2:B2-6. [PubMed:17650553 ]
  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. doi: 10.1021/ar800220p. [PubMed:19222207 ]
  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:17625839 ]
  4. Henness S, Keating GM: Gadofosveset. Drugs. 2006;66(6):851-7. [PubMed:16706555 ]
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Drug created on May 15, 2010 18:37 / Updated on July 29, 2016 01:52