Gadoxetic acid

Transporters (5)Biointeractions (5)

Identification

Name
Gadoxetic acid
Accession Number
DB08884
Type
Small Molecule
Groups
Approved
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
Similar Structures
Synonyms
  • Gadoxetate
  • Gadoxetic acid
  • Gd-EOB-DTPA
Product Ingredients
IngredientUNIICASInChI Key
Gadoxetate disodiumHOY74VZE0M135326-22-6SLYTULCOCGSBBJ-UHFFFAOYSA-I
Active Moieties
NameKindUNIICASInChI Key
Gadolinium cation (3+)ionicAZV954TZ9N22541-19-1RJOJUSXNYCILHH-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EovistInjection, solution181.43 mg/1mLIntravenousBayer2008-07-03Not applicableUs
PrimovistSolution181.43 mgIntravenousBayer2010-02-04Not applicableCanada
Categories
UNII
3QJA87N40S
CAS number
135326-11-3
Weight
Average: 681.75
Monoisotopic: 682.11214
Chemical Formula
C23H30GdN3O11
InChI Key
PCZHWPSNPWAQNF-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

Pharmacology

Indication

Gadoxetate is used as a contrast medium for magnetic resonance imaging (MRI) to detect and characterize lesions in the liver.

Associated Conditions
Pharmacodynamics

Gadoxetate 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 action

When 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.

Absorption
Not 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 elimination

Gadoxetate disodium is eliminated equally via urine and feces. Multidrug resistance protein 2 actively transports/excretes gadoxetate disodium into the bile.

Half life

Terminal 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

Toxicity

LD50, 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetylcysteineThe excretion of Gadoxetic acid can be decreased when combined with Acetylcysteine.
Aminohippuric acidThe excretion of Gadoxetic acid can be decreased when combined with Aminohippuric acid.
AmprenavirThe excretion of Gadoxetic acid can be decreased when combined with Amprenavir.
ApalutamideThe excretion of Gadoxetic acid can be increased when combined with Apalutamide.
AsunaprevirThe excretion of Gadoxetic acid can be decreased when combined with Asunaprevir.
AtalurenThe excretion of Gadoxetic acid can be decreased when combined with Ataluren.
AtazanavirThe excretion of Gadoxetic acid can be decreased when combined with Atazanavir.
AtorvastatinThe excretion of Gadoxetic acid can be decreased when combined with Atorvastatin.
AxitinibThe excretion of Gadoxetic acid can be decreased when combined with Axitinib.
BaricitinibThe excretion of Gadoxetic acid can be decreased when combined with Baricitinib.
Food Interactions
Not Available

References

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
KEGG Drug
D04288
PubChem Compound
131704314
PubChem Substance
175427133
ChemSpider
189907
ChEMBL
CHEMBL1201768
PharmGKB
PA165985534
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Gadoxetic_acid
ATC Codes
V08CA10 — Gadoxetic acid
AHFS Codes
  • 36:89.00* — Other Diagnostics
FDA label
Download (223 KB)
MSDS
Download (114 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0WithdrawnDiagnosticHepatocellular,Carcinoma1
1CompletedDiagnosticAdult Hepatocellular Carcinoma / Advanced Adult Hepatocellular Carcinoma / BCLC Stage 0 Adult Hepatocellular Carcinoma / BCLC Stage A Adult Hepatocellular Carcinoma / BCLC Stage B Adult Hepatocellular Carcinoma / BCLC Stage C Adult Hepatocellular Carcinoma / BCLC Stage D Adult Hepatocellular Carcinoma / Localized Non-Resectable Adult Liver Carcinoma / Localized Resectable Adult Liver Carcinoma1
2CompletedDiagnosticProstate Cancer1
3CompletedDiagnosticKnown or Suspected Focal Liver Lesions1
3TerminatedDiagnosticMagnetic Resonance Imaging (MRI)1
4Active Not RecruitingDiagnosticLiver Cirrhosis1
4CompletedDiagnosticContrast Media1
4CompletedDiagnosticHepatocellular,Carcinoma1
4CompletedDiagnosticTransient Severe Arterial Phase Motion1
4Not Yet RecruitingTreatmentMetastatic Hepatic Cancer / Primary Liver Cancers1
Not AvailableActive Not RecruitingNot AvailableDyspnea1
Not AvailableCompletedNot AvailableAdenoma benign / Carcinoma NOS / Hepatic abscess / Neoplasms, Hepatic1
Not AvailableCompletedNot AvailableDiagnostic Imaging1
Not AvailableCompletedNot AvailableHepatocellular,Carcinoma / Liver Dysfunction1
Not AvailableCompletedNot AvailableLiver Lesion / Neoplasms, Hepatic1
Not AvailableCompletedNot AvailableLivers1
Not AvailableRecruitingDiagnosticNeoplasms, Hepatic1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous181.43 mg/1mL
SolutionIntravenous181.43 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6039931No2000-03-212021-11-13Us
US5798092No1998-08-252015-08-25Us

Properties

State
Solid
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Transporters

Details1. Solute carrier organic anion transporter family member 1B1
Kind
Protein
Organism
Humans
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, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
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]
Details2. Solute carrier organic anion transporter family member 1B3
Kind
Protein
Organism
Humans
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), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
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]
Details3. Canalicular multispecific organic anion transporter 2
Kind
Protein
Organism
Humans
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 hepatocyte...
Gene Name
ABCC3
Uniprot ID
O15438
Uniprot Name
Canalicular multispecific organic anion transporter 2
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]
Details4. Canalicular multispecific organic anion transporter 1
Kind
Protein
Organism
Humans
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
Uniprot Name
Canalicular multispecific organic anion transporter 1
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]
Details5. Multidrug resistance-associated protein 4
Kind
Protein
Organism
Humans
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
Uniprot Name
Multidrug resistance-associated protein 4
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]

Drug created on May 22, 2013 15:49 / Updated on February 16, 2019 03:22