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Identification
- Summary
Gadobutrol is a gadolinium-based contrast agent (GBCA) used with contrasted magnetic resonance imaging (MRI) to detect and visualize lesions and abnormal vascularity.
- Brand Names
- Gadavist, Gadovist
- Generic Name
- Gadobutrol
- DrugBank Accession Number
- DB06703
- Background
Gadobutrol is a second-generation extracellular non-ionic macrocyclic GBCA (gadolinium-based contrast agent) used in magnetic resonance imaging (MRI) in adults and children older than 2 years of age. Due to its physicochemical properties, gadobutrol is formulated at twice the gadolinium ion concentration compared to other GBCA and thus requires a lesser injection volume.1
Like other GBCA, gadobutrol usage carries the risk of nephrogenic systemic fibrosis (NSF) due to the dissociation of gadolinium from the chelates, although gadobutrol tends to have a lower risk of NSF thanks to the macrocyclic structures that limit dechelation of gadolinium.1
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Gadobutrol (DB06703)
- Weight
- Average: 604.72
Monoisotopic: 605.13321 - Chemical Formula
- C18H31GdN4O9
- Synonyms
- Gadobutrol
- gadolinium(III) 2,2',2''-(10-((2R,3S )-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate
- External IDs
- BAY86-4875
- ZK-135079
Pharmacology
- Indication
Gadobutrol is indicated for use with magnetic resonance imaging for the following diagnostic processes:6
- To detect and visualize areas with disrupted blood-brain barrier and/or abnormal vascularity of the central nervous system in adult and pediatric patients, including term neonates.
- To assess the presence and extent of malignant breast disease in adult patients
- To evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients, including term neonates
- To assess myocardial perfusion (under stress and at rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Diagnostic process Arterial occlusive diseases of the supra-aortic arteries •••••••••••• •••••• ••••••••• ••••••••• ••••••••• Diagnostic process Cns abnormal vascularity •••••••••••• •••••• ••••••••• ••••••••• ••••••••• Diagnostic process Myocardial perfusion imaging •••••••••••• ••••• •••••••• •••••• ••••••• ••••• ••••••••• Diagnostic process Renal artery occlusion •••••••••••• •••••• ••••••••• ••••••••• ••••••••• Diagnostic process Malignant breast disease •••••••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
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Gadobutrol leads to distinct shortenings of relaxation times even in low concentrations. At pH 7, 37°C and 1.5 T, the relaxivity (r1) - determined from the influence on the relaxation times (T1) of protons in plasma - is 5.2 L/(mmol·sec) and the relaxivity (r2) - determined from the influence on the relaxation times (T2) - is 6.1 L/(mmol·sec). These relaxivities display only slight dependence on the strength of the magnetic field.6
- Mechanism of action
In MRI, visualization of normal and pathological tissue depends in part on variations in the radiofrequency signal intensity that occur with differences in proton density, the spin-lattice or longitudinal relaxation times (T1), and the spin-spin or transverse relaxation time (T2).6
When placed in a magnetic field, gadobutrol shortens the T1 and T2 relaxation times. The extent of decrease of T1 and T2 relaxation times, and therefore the amount of signal enhancement obtained from gadobutrol, is based upon several factors including the concentration of gadobutrol in the tissue, the field strength of the MRI system, and the relative ratio of the longitudinal and transverse relaxation times. At the recommended dose, the T1 shortening effect is observed with the greatest sensitivity in T1-weighted magnetic resonance sequences. In T2*-weighted sequences, the induction of local magnetic field inhomogeneities by the large magnetic moment of gadolinium and at high concentrations (during bolus injection) leads to a signal decrease.6
- Absorption
After intravenous administration, gadobutrol is rapidly distributed in the extracellular space. After a gadobutrol dose of 0.1 mmol/kg body weight, an average level of 0.59 mmol gadobutrol/L was measured in plasma 2 minutes after the injection and 0.3 mmol gadobutrol/L 60 minutes after the injection. Gadobutrol does not display any particular protein binding. Following GBCA administration, gadolinium is present for months or years in the brain, bone, skin, and other organs.6
The mean AUC of gadobutrol in patients with normal renal function was 1.1 ± 0.1 mmol∙h/L, compared to 4.0 ± 1.8 mmol∙h/L in patients with mild to moderate renal impairment and 11.5 ± 4.3 mmol∙h/L in patients with severe renal impairment.6
- Volume of distribution
In children aged 2 to 17, the body weight-normalized median total volumes of distribution (L/kg) were estimated to be 0.20 (0.12, 0.28) for all ages, 0.24 (0.20, 0.28) in the 2 to 6-year age group, 0.19 (0.14, 0.23) in the 7 to 11 year age group and 0.18 (0.092, 0.23) in the 12 to 17 year age group.4
- Protein binding
No information is available on the protein binding of gadobutrol.
- Metabolism
Gadobutrol is not metabolized.6
- Route of elimination
Gadobutrol is excreted in an unchanged form via the kidneys. Within two hours after intravenous administration more than 50% and within 12 hours more than 90% of the given dose is eliminated via the urine. Extra-renal elimination is negligible.6
- Half-life
For adult patients, the half-life was estimated to be 1.80 (1.20, 6.55) hours. For pediatric aged 0 to <2 years, 2 to 6 years, 7 to 11 years, and 12 to < 18 years, the half-life was calculated to be 2.91 (1.60, 12.4), 1.91 (1.04, 2.70), 1.66 (0.91, 2.71), and 1.68 (1.31, 2.48) hours respectively.6
- Clearance
In healthy subjects, renal clearance is 1.1 - 1.7mL/(min·kg). Clearance was observed to be slightly lower in elderly subjects, when using a 0.1 mmol/kg dose.6
- Adverse Effects
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GBCAs cross the placenta and result in fetal exposure and gadolinium retention. The human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive. In animal reproduction studies, although teratogenicity was not observed, embryo-lethality was observed in monkeys, rabbits, and rats receiving intravenous gadobutrol during organogenesis at doses 8 times and above the recommended human dose. Retardation of embryonal development was observed in rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 and 12 times, respectively, the recommended human dose. Because of the potential risks of gadolinium to the fetus, use Gadavist only if imaging is essential during pregnancy and cannot be delayed.6
The maximum dose of gadobutrol tested in healthy volunteers, 1.5 mL/kg body weight (1.5 mmol/kg; 15 times the recommended dose), was tolerated in a manner similar to lower doses. Gadobutrol can be removed by hemodialysis [
No carcinogenicity studies of gadobutrol have been conducted.6
Gadobutrol was not mutagenic in in vitro reverse mutation tests in bacteria, in the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) test using cultured Chinese hamster V79 cells, or in chromosome aberration tests in human peripheral blood lymphocytes, and was negative in an in vivo micronucleus test in mice after intravenous injection of 0.5 mmol/kg.6
Gadobutrol had no effect on fertility and general reproductive performance of male and female rats when given in doses 12.2 times the human equivalent dose (based on body surface area).6
Local intolerance reactions, including moderate irritation associated with infiltration of inflammatory cells was observed after paravenous administration to rabbits, suggesting the possibility of occurrence of local irritation if the contrast medium leaks around veins in a clinical setting.6
- 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.No interactions found.
- Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Active Moieties
Name Kind UNII CAS InChI Key Gadolinium cation (3+) ionic AZV954TZ9N 22541-19-1 RJOJUSXNYCILHH-UHFFFAOYSA-N - International/Other Brands
- Gadovist (Bayer Schering Pharma)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Gadavist Injection 604.72 mg/1mL Intravenous Bayer HealthCare Pharmaceuticals Inc. 2011-03-14 Not applicable US 
Gadovist 1.0 Solution 604.72 mg / mL Intravenous Bayer 2004-01-30 Not applicable Canada 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Gadobutrol Injection 604.72 mg/1mL Intravenous Slate Run Pharmaceuticals, Llc 2023-06-01 Not applicable US Gadobutrol Injection 604.72 mg/1mL Intravenous Fresenius Kabi USA, LLC 2023-10-01 Not applicable US Gadobutrol Injection 604.72 mg/1mL Intravenous Slate Run Pharmaceuticals, Llc 2023-10-20 Not applicable US Gadobutrol Injection 604.72 mg/1mL Intravenous Fresenius Kabi USA, LLC 2023-04-14 Not applicable US Gadobutrol Injection 604.72 mg/1mL Intravenous Fresenius Kabi USA, LLC 2023-10-01 Not applicable US
Categories
- ATC Codes
- V08CA09 — Gadobutrol
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alpha amino acids. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon).
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Alpha amino acids
- Alternative Parents
- Tricarboxylic acids and derivatives / 1,3-aminoalcohols / Trialkylamines / Secondary alcohols / 1,2-aminoalcohols / Amino acids / Carboxylic acid salts / Polyols / Azacyclic compounds / Carboxylic acids show 7 more
- Substituents
- 1,2-aminoalcohol / 1,3-aminoalcohol / Alcohol / Aliphatic heteromonocyclic compound / Alpha-amino acid / Amine / Amino acid / Azacycle / Carbonyl group / Carboxylic acid show 17 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- gadolinium coordination entity (CHEBI:68841)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1BJ477IO2L
- CAS number
- 770691-21-9
- InChI Key
- ZPDFIIGFYAHNSK-YYLIZZNMSA-K
- InChI
- InChI=1S/C18H34N4O9.Gd/c23-12-14(15(25)13-24)22-7-5-20(10-17(28)29)3-1-19(9-16(26)27)2-4-21(6-8-22)11-18(30)31;/h14-15,23-25H,1-13H2,(H,26,27)(H,28,29)(H,30,31);/q;+3/p-3/t14-,15-;/m0./s1
- IUPAC Name
- 4,7,10-tris(carboxymethyl)-1-[(2S,3R)-1,3,4-trihydroxybutan-2-yl]-1,4,7,10-tetraaza-13-gadolinatetracyclo[5.5.1.0^{4,13}.0^{10,13}]tridecane-1,4,7,10-tetraium-13-uide
- SMILES
- OC[C@H](O)[C@H](CO)[N+]12CC[N+]3(CC([O-])=O)CC[N+]4(CC([O-])=O)CC[N+](CC([O-])=O)(CC1)[Gd-]234
References
- Synthesis Reference
Orlin Petrov, Peter Blaszkiewicz, "Process for mono- and 1,7-bis-N-.beta.-hydroxyalkylation of cyclene; N-.beta.-hydroxyalkyl-1,4,7,10-tetraazacyclododecane-lithium-salt complexes and the use of the complexes for the production of gadobutrol and analogs." U.S. Patent US5994536, issued May, 1998.
US5994536- General References
- Scott LJ: Gadobutrol: a review of its use for contrast-enhanced magnetic resonance imaging in adults and children. Clin Drug Investig. 2013 Apr;33(4):303-14. doi: 10.1007/s40261-013-0066-0. [Article]
- Wack C, Steger-Hartmann T, Mylecraine L, Hofmeister R: Toxicological safety evaluation of gadobutrol. Invest Radiol. 2012 Nov;47(11):611-23. doi: 10.1097/RLI.0b013e318263f128. [Article]
- Kunnemeyer J, Terborg L, Nowak S, Scheffer A, Telgmann L, Tokmak F, Gunsel A, Wiesmuller G, Reichelt S, Karst U: Speciation analysis of gadolinium-based MRI contrast agents in blood plasma by hydrophilic interaction chromatography/electrospray mass spectrometry. Anal Chem. 2008 Nov 1;80(21):8163-70. doi: 10.1021/ac801264j. Epub 2008 Sep 27. [Article]
- Hahn G, Sorge I, Gruhn B, Glutig K, Hirsch W, Bhargava R, Furtner J, Born M, Schroder C, Ahlstrom H, Kaiser S, Moritz JD, Kunze CW, Shroff M, Stokland E, Trnkova ZJ, Schultze-Mosgau M, Reif S, Bacher-Stier C, Mentzel HJ: Pharmacokinetics and safety of gadobutrol-enhanced magnetic resonance imaging in pediatric patients. Invest Radiol. 2009 Dec;44(12):776-83. doi: 10.1097/RLI.0b013e3181bfe2d2. [Article]
- FDA Approved Drug Products: Gadavist (gadobutrol) injection for intravenous administration [Link]
- FDA Approved Drug Products: GADAVIST (gadobutrol) injection, for intravenous use (Feb 2024) [Link]
- External Links
- Human Metabolome Database
- HMDB0015649
- KEGG Drug
- D07420
- PubChem Compound
- 70678987
- PubChem Substance
- 99443257
- ChemSpider
- 28533281
- 84990
- ChEBI
- 68841
- ChEMBL
- CHEMBL2218860
- PharmGKB
- PA165958377
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Gadobutrol
- FDA label
- Download (103 KB)
- MSDS
- Download (40.2 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Diagnostic Hepatic Metastases / Hepatocellular Carcinoma / Liver and Intrahepatic Bile Duct Disorder / Primary Malignant Liver Neoplasm 1 somestatus stop reason just information to hide Not Available Completed Not Available Contrast Enhancement in Magnetic Resonance Imaging 1 somestatus stop reason just information to hide Not Available Completed Not Available Epidemiologic Factors 1 somestatus stop reason just information to hide Not Available Completed Not Available Image Enhancement / Magnetic Resonance Imaging (MRI) 1 somestatus stop reason just information to hide Not Available Completed Not Available Magnetic Resonance Angiography / Magnetic Resonance Imaging (MRI) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 604.72 mg/1mL Injection, solution Parenteral Injection, solution Injection Intravenous 0.5 MMOL/ML Injection Intravenous 1 MMOL/ML Injection, solution 604.72 mg Injection, solution Intravenous 0.5 MMOL/ML Injection, solution Intravenous 1 MMOL/ML Injection, solution Parenteral 1 MMOL/ML Injection, solution Parenteral 1.0 MMOL/ML Solution Intravenous 604.72 mg/1ml Solution Intravenous 604.72 mg / mL Solution Intravenous 604.72 mg/ml Injection, solution Intravenous Injection Intravenous 604.72 mg Injection Intravenous 604.720 mg Solution Intravenous 1 mmol Injection, solution 1.0 mmol/ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5980864 No 1999-11-09 2016-11-09 US
Properties
- State
- Liquid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0496 mg/mL ALOGPS logP 0.35 ALOGPS logP -4.6 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 0.99 Chemaxon pKa (Strongest Basic) -3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 9 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 181.08 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 143.47 m3·mol-1 Chemaxon Polarizability 45.39 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.9703 Blood Brain Barrier - 0.7581 Caco-2 permeable - 0.7342 P-glycoprotein substrate Substrate 0.7464 P-glycoprotein inhibitor I Non-inhibitor 0.9204 P-glycoprotein inhibitor II Non-inhibitor 0.9222 Renal organic cation transporter Non-inhibitor 0.8783 CYP450 2C9 substrate Non-substrate 0.9002 CYP450 2D6 substrate Non-substrate 0.8025 CYP450 3A4 substrate Non-substrate 0.731 CYP450 1A2 substrate Non-inhibitor 0.8461 CYP450 2C9 inhibitor Non-inhibitor 0.8755 CYP450 2D6 inhibitor Non-inhibitor 0.9271 CYP450 2C19 inhibitor Non-inhibitor 0.8538 CYP450 3A4 inhibitor Non-inhibitor 0.8888 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9958 Ames test Non AMES toxic 0.6773 Carcinogenicity Non-carcinogens 0.9472 Biodegradation Not ready biodegradable 0.561 Rat acute toxicity 2.2102 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8805 hERG inhibition (predictor II) Non-inhibitor 0.7963
Spectra
- Mass Spec (NIST)
- Download (21.2 KB)
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-08gi-4109200000-e2cb64efbe4b4b47d094 - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Drug created at May 15, 2010 17:36 / Updated at September 15, 2024 04:38