Gadofosveset trisodium

Identification

Name
Gadofosveset trisodium
Accession Number
DB06705
Type
Small Molecule
Groups
Approved
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 IDs
MS-325
Product Ingredients
IngredientUNIICASInChI Key
Gadofosveset trisodium monohydrateXM33Q67UVH211570-55-7PIZALBORPSCYJU-QSQMUHTISA-H
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AblavarInjection, solution244 mg/mLIntravenousLantheus Medical Imaging2008-12-122017-01-12Us
AblavarSolution244 mgIntravenousLantheus Mi Canada Inc2010-10-122016-03-07Canada
VasovistSolution244 mgIntravenousBayer2007-08-202009-08-06Canada
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AblavarInjection, solution0.25 mmol/mlIntravenousTmc Pharma Services Ltd.2005-10-03Not applicableEu
AblavarInjection, solution0.25 mmol/mlIntravenousTmc Pharma Services Ltd.2005-10-03Not applicableEu
AblavarInjection, solution0.25 mmol/mlIntravenousTmc Pharma Services Ltd.2005-10-03Not applicableEu
AblavarInjection, solution0.25 mmol/mlIntravenousTmc Pharma Services Ltd.2005-10-03Not applicableEu
AblavarInjection, solution0.25 mmol/mlIntravenousTmc Pharma Services Ltd.2005-10-03Not applicableEu
AblavarInjection, solution0.25 mmol/mlIntravenousTmc Pharma Services Ltd.2005-10-03Not applicableEu
AblavarInjection, solution0.25 mmol/mlIntravenousTmc Pharma Services Ltd.2005-10-03Not applicableEu
AblavarInjection, solution0.25 mmol/mlIntravenousTmc Pharma Services Ltd.2005-10-03Not applicableEu
AblavarInjection, solution0.25 mmol/mlIntravenousTmc Pharma Services Ltd.2005-10-03Not applicableEu
Categories
UNII
9430ZR8ZAN
CAS number
193901-90-5
Weight
Average: 957.87
Monoisotopic: 958.10256
Chemical Formula
C33H38GdN3Na3O14P
InChI Key
XGOSYNSWSRUASG-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

Pharmacology

Indication

Gadofosveset 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.

Structured Indications
Pharmacodynamics

Gadofosveset 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 action

Gadofosveset 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.

Absorption
Not Available
Volume of distribution

48 ± 16 mL/kg

Protein binding

80-90%

Metabolism

Gadofosveset does not undergo measurable metabolism.

Route of elimination

Gadofosveset 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 life

18.5 hours

Clearance

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

Toxicity

Gadolinium-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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

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
KEGG Drug
D04286
PubChem Compound
73049652
PubChem Substance
175427086
ChemSpider
58829621
ChEMBL
CHEMBL1908362
PharmGKB
PA165958378
Drugs.com
Drugs.com Drug Page
Wikipedia
Gadofosveset
ATC Codes
V08CA11 — Gadofosveset
FDA label
Download (148 KB)
MSDS
Download (66.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedDiagnosticAtherosclerosis / Chronic Total Aterial Occlusion / Intermittent Claudication / Peripheral Artery Disease (PAD)1
2CompletedDiagnosticMyocardial Ischemia1
3CompletedDiagnosticPeripheral Vascular Disease (PVD)1
3CompletedDiagnosticSteno-Occlusive Disease1
4CompletedDiagnosticChronic Liver Diseases (CLD)1
4RecruitingDiagnosticPediatric Congenital Heart Disease1
4Unknown StatusDiagnosticCongenital Heart Disease (CHD)1
4WithdrawnDiagnosticNeoplasms, Ovarian1
Not AvailableCompletedNot AvailableMagnetic Resonance Imaging (MRI) / Neoplasms Staging / Rectal Neoplasms1
Not AvailableCompletedNot AvailableNephrogenic Systemic Fibrosis1
Not AvailableCompletedNot AvailableProphylaxis of Pulmonary embolism1
Not AvailableCompletedDiagnosticHealthy Volunteers1
Not AvailableTerminatedDiagnosticNeoplasms, Breast1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous0.25 mmol/ml
Injection, solutionIntravenous244 mg/mL
SolutionIntravenous244 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2304461No2008-10-142018-08-17Canada
CA2211100No2007-03-202016-01-16Canada
US6676929No2000-05-042020-05-04Us

Properties

State
Solid
Experimental Properties
Not 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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Taxonomy

Classification
Not classified

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 colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
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]

Drug created on May 15, 2010 18:37 / Updated on November 09, 2017 03:55