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Identification
NameGadoxetic acid
Accession NumberDB08884
TypeSmall Molecule
GroupsApproved
Description

Gadoxetic acid (gadoxetate) is a paramagnetic gadolinium-containing contrast agent in which its salt form, gadoxetate disodium, is used for intravenous injection. Ethoxybenzyl diethylenetriaminepentaacetic acid is the moiety that chelates with a gadolinium ion and forms a stable complex with it to make up the drug. It is marketed by Bayer HealthCare Pharmaceuticals and FDA approved on July 3, 2008.

Structure
Thumb
Synonyms
Gadoxetate
Gd-EOB-DTPA
External Identifiers
  • SHL-569B
  • ZK-139834
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Eovistinjection, solution181.43 mg/mLintravenousBayer Health Care Pharmaceuticals Inc.2008-07-03Not applicableUs
Primovistsolution181.43 mgintravenousBayer Inc2010-02-04Not applicableCanada
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
Gadoxetate disodium
135326-22-6
Thumb
  • InChI Key: SLYTULCOCGSBBJ-UHFFFAOYSA-I
  • Monoisotopic Mass: 726.076023636
  • Average Mass: 725.71
DBSALT000091
Categories
UNII3QJA87N40S
CAS number135326-11-3
WeightAverage: 681.75
Monoisotopic: 682.11214
Chemical FormulaC23H30GdN3O11
InChI KeyPCZHWPSNPWAQNF-LMOVPXPDSA-K
InChI
InChI=1S/C23H33N3O11.Gd/c1-2-37-18-5-3-16(4-6-18)9-17(26(14-22(33)34)15-23(35)36)10-24(11-19(27)28)7-8-25(12-20(29)30)13-21(31)32;/h3-6,17H,2,7-15H2,1H3,(H,27,28)(H,29,30)(H,31,32)(H,33,34)(H,35,36);/q;+3/p-3/t17-;/m0./s1
IUPAC Name
gadolinium(3+) ion 2-[(2-{[(2S)-2-[bis(carboxymethyl)amino]-3-(4-ethoxyphenyl)propyl](carboxylatomethyl)amino}ethyl)(carboxylatomethyl)amino]acetate
SMILES
[Gd+3].[H][C@@](CN(CCN(CC([O-])=O)CC([O-])=O)CC([O-])=O)(CC1=CC=C(OCC)C=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
  • Alpha-amino acid
  • Alpha-amino acid or derivatives
  • Amphetamine or derivatives
  • Phenoxy compound
  • Phenol ether
  • Alkyl aryl ether
  • Aralkylamine
  • Benzenoid
  • Monocyclic benzene moiety
  • Amino acid or derivatives
  • Tertiary aliphatic amine
  • Tertiary amine
  • Amino acid
  • Carboxylic acid salt
  • Carboxylic acid
  • Ether
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Organic zwitterion
  • Amine
  • Organic oxygen compound
  • Organic salt
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationGadoxetate is used as a contrast medium for magnetic resonance imaging (MRI) to detect and characterize lesions in the liver.
PharmacodynamicsGadoxetate disodium is an amphipathic compound in which gadoxetate is hydrophillic and its moiety, the ethoxybenyzl group, is lipophillic. Consequently, gadoxetate disodium has a biphasic mode of action in which it first distributes into the extracellular space after bolus injection and then hepatocytes selectively takes up the drug.
Mechanism of actionWhen gadoxetate disodium is placed in an external magnetic field, a large magnetic moment is produced. As a result, a magnetic field is induced around the tissue. The water protons in the vicinity are disrupted such that the change the proton density and spin characteristics are detected and visualized by a device.
Related Articles
AbsorptionNot Available
Volume of distribution

Total volume of distribution at steady state is 0.21 L/kg. Gadoxetate disodium cannot diffuse through the blood brain barrier. The two transporters that gadoxetate disodium can enter the hepatocyte through are OATP1B1 and OATP1B3. Gadoxetate disodium may also exit the heptaocyte and go back into sinusoidal space via active transport through multidrug resistance protein 3 and 4.

Protein binding<10% protein bound. Because it is more protein bound than other gadolinium-based contrast agents, gadoxetate disodium has increased T1 relaxivity. This results in an enhancement of the signal.
Metabolism

Gadoxetate disodium is not metabolized.

Route of eliminationGadoxetate disodium is eliminated equally via urine and feces. Multidrug resistance protein 2 actively transports/excretes gadoxetate disodium into the bile.
Half lifeTerminal elimination half-life, healthy subjects, adults = 0.91 - 0.95 hours
Clearance

Clearance may be lower in older patients.
Total serum clearance (CLtot) = 250 mL/min;
Renal clearance (CLr) = 120 mL/min

ToxicityLD50, oral, rat = 18100 mg/kg; LD50, oral, mouse = 14500 mg/kg; LD50, IV, rat = 3600 - 7300 mg/kg; LD50, IV, mouse = 5400 - 10900 mg/kg; LD50, IV, dog = >2200 mg/kg
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+0.6058
Blood Brain Barrier+0.6251
Caco-2 permeable-0.5137
P-glycoprotein substrateSubstrate0.6927
P-glycoprotein inhibitor INon-inhibitor0.6538
P-glycoprotein inhibitor IINon-inhibitor0.9495
Renal organic cation transporterNon-inhibitor0.6488
CYP450 2C9 substrateNon-substrate0.8375
CYP450 2D6 substrateNon-substrate0.8177
CYP450 3A4 substrateNon-substrate0.6054
CYP450 1A2 substrateNon-inhibitor0.6386
CYP450 2C9 inhibitorNon-inhibitor0.7982
CYP450 2D6 inhibitorNon-inhibitor0.6855
CYP450 2C19 inhibitorNon-inhibitor0.781
CYP450 3A4 inhibitorNon-inhibitor0.9528
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7762
Ames testNon AMES toxic0.6871
CarcinogenicityNon-carcinogens0.8385
BiodegradationNot ready biodegradable0.6465
Rat acute toxicity2.2477 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5
hERG inhibition (predictor II)Non-inhibitor0.7809
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, solutionintravenous181.43 mg/mL
Solutionintravenous181.43 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5798092 No1995-08-252015-08-25Us
US6039931 No2001-11-132021-11-13Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
pKa6.8-8MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.497 mg/mLALOGPS
logP1.24ALOGPS
logP-4.3ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)1.98ChemAxon
pKa (Strongest Basic)9.99ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area213.94 Å2ChemAxon
Rotatable Bond Count20ChemAxon
Refractivity159.21 m3·mol-1ChemAxon
Polarizability50.67 Å3ChemAxon
Number of Rings1ChemAxon
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. Van Beers BE, Pastor CM, Hussain HK: Primovist, Eovist: what to expect? J Hepatol. 2012 Aug;57(2):421-9. doi: 10.1016/j.jhep.2012.01.031. Epub 2012 Apr 12. [PubMed:22504332 ]
External Links
ATC CodesV08CA10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (223 KB)
MSDSDownload (114 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
References
  1. Nassif A, Jia J, Keiser M, Oswald S, Modess C, Nagel S, Weitschies W, Hosten N, Siegmund W, Kuhn JP: Visualization of hepatic uptake transporter function in healthy subjects by using gadoxetic acid-enhanced MR imaging. Radiology. 2012 Sep;264(3):741-50. doi: 10.1148/radiol.12112061. Epub 2012 Jul 6. [PubMed:22771883 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular Weight:
77402.175 Da
References
  1. Nassif A, Jia J, Keiser M, Oswald S, Modess C, Nagel S, Weitschies W, Hosten N, Siegmund W, Kuhn JP: Visualization of hepatic uptake transporter function in healthy subjects by using gadoxetic acid-enhanced MR imaging. Radiology. 2012 Sep;264(3):741-50. doi: 10.1148/radiol.12112061. Epub 2012 Jul 6. [PubMed:22771883 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Organic anion transmembrane transporter activity
Specific Function:
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity).
Gene Name:
ABCC3
Uniprot ID:
O15438
Molecular Weight:
169341.14 Da
References
  1. Van Beers BE, Pastor CM, Hussain HK: Primovist, Eovist: what to expect? J Hepatol. 2012 Aug;57(2):421-9. doi: 10.1016/j.jhep.2012.01.031. Epub 2012 Apr 12. [PubMed:22504332 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular Weight:
174205.64 Da
References
  1. Van Beers BE, Pastor CM, Hussain HK: Primovist, Eovist: what to expect? J Hepatol. 2012 Aug;57(2):421-9. doi: 10.1016/j.jhep.2012.01.031. Epub 2012 Apr 12. [PubMed:22504332 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Atpase activity, coupled to transmembrane movement of substances
Specific Function:
May be an organic anion pump relevant to cellular detoxification.
Gene Name:
ABCC4
Uniprot ID:
O15439
Molecular Weight:
149525.33 Da
References
  1. Van Beers BE, Pastor CM, Hussain HK: Primovist, Eovist: what to expect? J Hepatol. 2012 Aug;57(2):421-9. doi: 10.1016/j.jhep.2012.01.031. Epub 2012 Apr 12. [PubMed:22504332 ]
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Drug created on May 22, 2013 15:49 / Updated on May 31, 2016 02:12