Gadoxetic acid
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
- 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 Eovist Injection, solution 181.43 mg/1mL Intravenous Bayer 2008-07-03 Not applicable US Primovist Solution 181.43 mg Intravenous Bayer 2010-02-04 Not applicable Canada - Categories
- Acetates
- Acids, Acyclic
- Amines
- Contrast Media
- Diagnostic Uses of Chemicals
- Fatty Acids
- Fatty Acids, Volatile
- Gadolinium-based Contrast Agent
- Lipids
- Magnetic Resonance Contrast Activity
- Magnetic Resonance Imaging Contrast Media
- OATP1B1/SLCO1B1 Substrates
- OATP1B3 substrates
- Organometallic Compounds
- Other Diagnostics
- Paramagnetic Contrast Agent
- Paramagnetic Contrast Media
- Pentetic Acid
- Polyamines
- 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
Drug Interaction 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. - 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
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Injection, solution Intravenous 181.43 mg/1mL Solution Intravenous 181.43 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) US6039931 No 2000-03-21 2021-11-13 US US5798092 No 1998-08-25 2015-08-25 US
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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Taxonomy
- Classification
- Not classified
Transporters
- 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]
- 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]
- 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]
- 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]
- 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 February 18, 2019 20:23