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

Similar Structures

Synonyms

Gadoxetate
Gadoxetic acid
Gd-EOB-DTPA

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Gadoxetate disodium	HOY74VZE0M	135326-22-6	SLYTULCOCGSBBJ-UHFFFAOYSA-I

Active Moieties

Name	Kind	UNII	CAS	InChI Key
Gadolinium cation (3+)	ionic	AZV954TZ9N	22541-19-1	RJOJUSXNYCILHH-UHFFFAOYSA-N

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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Eovist	Injection, solution	181.43 mg/1mL	Intravenous	Bayer HealthCare Pharmaceuticals Inc.	2008-07-03	Not applicable
Primovist	Solution		Intravenous	Bayer	2010-02-04	Not applicable

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

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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

Chronic Liver Diseases (CLD)

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.

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Adverse Effects

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Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

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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

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Acetylcysteine	The excretion of Gadoxetic acid can be decreased when combined with Acetylcysteine.
Aminohippuric acid	The excretion of Gadoxetic acid can be decreased when combined with Aminohippuric acid.
Amprenavir	The excretion of Gadoxetic acid can be decreased when combined with Amprenavir.
Apalutamide	The excretion of Gadoxetic acid can be increased when combined with Apalutamide.
Asunaprevir	The excretion of Gadoxetic acid can be decreased when combined with Asunaprevir.
Ataluren	The excretion of Gadoxetic acid can be decreased when combined with Ataluren.
Atazanavir	The excretion of Gadoxetic acid can be decreased when combined with Atazanavir.
Atorvastatin	The excretion of Gadoxetic acid can be decreased when combined with Atorvastatin.
Axitinib	The excretion of Gadoxetic acid can be decreased when combined with Axitinib.
Baricitinib	The excretion of Gadoxetic acid can be decreased when combined with Baricitinib.

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Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

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Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

Not Available

References

General References

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

Phase	Status	Purpose	Conditions	Count
0	Recruiting	Diagnostic	Castration-Resistant Prostate Cancer (CRPC) / Prostate Cancer	1
0	Withdrawn	Diagnostic	Hepatocellular,Carcinoma	1
1	Completed	Diagnostic	Adult 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 Carcinoma	1
1, 2	Completed	Basic Science	Drug Transporter / Gd-EOB-DTPA / Livers / MRI of liver / Pharmacokinetics	1
2	Completed	Diagnostic	Prostate Cancer	1
3	Completed	Diagnostic	Known or Suspected Focal Liver Lesions	1
3	Terminated	Diagnostic	Magnetic Resonance Imaging (MRI)	1
4	Active Not Recruiting	Diagnostic	Liver Cirrhosis	1
4	Completed	Diagnostic	Contrast Media	1
4	Completed	Diagnostic	Hepatocellular,Carcinoma	1
4	Completed	Diagnostic	Transient Severe Arterial Phase Motion	1
4	Not Yet Recruiting	Treatment	Metastatic Hepatic Cancer / Primary Liver Cancers	1
Not Available	Active Not Recruiting	Not Available	Dyspnea	1
Not Available	Completed	Not Available	Adenoma benign / Carcinoma NOS / Hepatic abscess / Neoplasms, Hepatic	1
Not Available	Completed	Not Available	Diagnostic Imaging	1
Not Available	Completed	Not Available	Hepatocellular,Carcinoma / Liver Dysfunction	1
Not Available	Completed	Not Available	Liver Lesion / Neoplasms, Hepatic	1
Not Available	Completed	Not Available	Livers	1
Not Available	Recruiting	Diagnostic	Hepatocellular,Carcinoma / Liver and Intrahepatic Bile Duct Disorder / Metastatic Malignant Neoplasm in the Liver / Neoplasms, Hepatic / Primary Malignant Liver Neoplasm	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Form	Route	Strength
Injection, solution	Intravenous	181.43 mg/1mL
Solution	Intravenous

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
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US6039931	No	2000-03-21	2021-11-13
US5798092	No	1998-08-25	2015-08-25

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Filed On

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Properties

State

Solid

Experimental Properties

Property	Value	Source
pKa	6.8-8	MSDS

Predicted Properties

Property	Value	Source
Water Solubility	0.497 mg/mL	ALOGPS
logP	1.24	ALOGPS
logP	-4.3	ChemAxon
logS	-3.2	ALOGPS
pKa (Strongest Acidic)	1.98	ChemAxon
pKa (Strongest Basic)	9.99	ChemAxon
Physiological Charge	-3	ChemAxon
Hydrogen Acceptor Count	14	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	213.94 Å²	ChemAxon
Rotatable Bond Count	20	ChemAxon
Refractivity	159.21 m³·mol^-1	ChemAxon
Polarizability	50.67 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.6058
Blood Brain Barrier	+	0.6251
Caco-2 permeable	-	0.5137
P-glycoprotein substrate	Substrate	0.6927
P-glycoprotein inhibitor I	Non-inhibitor	0.6538
P-glycoprotein inhibitor II	Non-inhibitor	0.9495
Renal organic cation transporter	Non-inhibitor	0.6488
CYP450 2C9 substrate	Non-substrate	0.8375
CYP450 2D6 substrate	Non-substrate	0.8177
CYP450 3A4 substrate	Non-substrate	0.6054
CYP450 1A2 substrate	Non-inhibitor	0.6386
CYP450 2C9 inhibitor	Non-inhibitor	0.7982
CYP450 2D6 inhibitor	Non-inhibitor	0.6855
CYP450 2C19 inhibitor	Non-inhibitor	0.781
CYP450 3A4 inhibitor	Non-inhibitor	0.9528
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.7762
Ames test	Non AMES toxic	0.6871
Carcinogenicity	Non-carcinogens	0.8385
Biodegradation	Not ready biodegradable	0.6465
Rat acute toxicity	2.2477 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.5
hERG inhibition (predictor II)	Non-inhibitor	0.7809

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

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

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

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

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

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 December 06, 2019 12:02

Gadoxetic acid

Identification

Structure for Gadoxetic acid (DB08884)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Transporters

References

References

References

References

References