Gadodiamide

Identification

Name
Gadodiamide
Accession Number
DB00225  (APRD00990)
Type
Small Molecule
Groups
Approved, Investigational
Description

Gadodiamide is a gadolinium based contrast agent used in MR imaging procedures to assist in the visualization of blood vessels. It is commonly marketed under the trade name Omniscan.

Structure
Thumb
Synonyms
  • Gadodiamida
  • Gadodiamide anhydrous
External IDs
S-041
Product Ingredients
IngredientUNIICASInChI Key
Gadodiamide hydrate0RPE15QPL0122795-43-1XPCLDSMKWNNKOM-UHFFFAOYSA-K
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OmniscanInjection287 mg/1mLIntravenousGE Healthcare Inc.2006-09-21Not applicableUs
OmniscanSolution287 mgIntravenousGe Healthcare1997-03-25Not applicableCanada
OmniscanInjection287 mg/1mLIntravenousGE Healthcare Inc.2002-04-19Not applicableUs
Omniscan Liq IV 287mg/mlLiquid287 mgIntravenousSanofi1994-12-311997-07-30Canada
Categories
UNII
84F6U3J2R6
CAS number
131410-48-5
Weight
Average: 573.66
Monoisotopic: 574.10225
Chemical Formula
C16H26GdN5O8
InChI Key
HZHFFEYYPYZMNU-UHFFFAOYSA-K
InChI
InChI=1S/C16H29N5O8.Gd/c1-17-12(22)7-20(10-15(26)27)5-3-19(9-14(24)25)4-6-21(11-16(28)29)8-13(23)18-2;/h3-11H2,1-2H3,(H,17,22)(H,18,23)(H,24,25)(H,26,27)(H,28,29);/q;+3/p-3
IUPAC Name
19,22-bis(methylamino)-3,13,16-trioxo-2λ³,14λ³,15λ³-trioxa-20λ³,23λ³-dioxa-5λ⁴,8λ⁴,11λ⁴-triaza-1-gadolinaheptacyclo[6.6.3.3¹,⁵.3¹,¹¹.0¹,⁵.0¹,⁸.0¹,¹¹]tricosa-19,22-diene-1,1,1-tris(ylium)-2,14,15-triide
SMILES
O=C1[O-][Gd+3]234567[O]=C(C[N]2(CC[N]3(CC([O-]4)=O)CC[N]5(CC(=[O]6)NC)CC(=O)[O-]7)C1)NC

Pharmacology

Indication

For intravenous use in MRI to visualize lesions with abnormal vascularity (or those thought to cause abnormalities in the blood-brain barrier) in the brain (intracranial lesions), spine, and associated tissues.

Pharmacodynamics
Not Available
Mechanism of action

Based on the behavior of protons when placed in a strong magnetic field, which is interpreted and transformed into images by magnetic resonance (MR) instruments. Paramagnetic agents have unpaired electrons that generate a magnetic field about 700 times larger than the proton's field, thus disturbing the proton's local magnetic field. When the local magnetic field around a proton is disturbed, its relaxation process is altered. MR images are based on proton density and proton relaxation dynamics. MR instruments can record 2 different relaxation processes, the T1 (spin-lattice or longitudinal relaxation time) and the T2 (spin-spin or transverse relaxation time). In magnetic resonance imaging (MRI), visualization of normal and pathological brain tissue depends in part on variations in the radiofrequency signal intensity that occur with changes in proton density, alteration of the T1, and variation in the T2. When placed in a magnetic field, gadodiamide shortens both the T1 and the T2 relaxation times in tissues where it accumulates. At clinical doses, gadodiamide primarily affects the T1 relaxation time, thus producing an increase in signal intensity. Gadodiamide does not cross the intact blood-brain barrier; therefore, it does not accumulate in normal brain tissue or in central nervous system (CNS) lesions that have not caused an abnormal blood-brain barrier (e.g., cysts, mature post-operative scars). Abnormal vascularity or disruption of the blood-brain barrier allows accumulation of gadodiamide in lesions such as neoplasms, abscesses, and subacute infarcts.

Absorption
Not Available
Volume of distribution
  • 200 ± 61 mL/kg
Protein binding
Not Available
Metabolism

There is no detectable biotransformation or decomposition of gadodiamide.

Route of elimination

Gadodiamide is eliminated primarily in the urine.

Half life

Two-compartment model with mean distribution and elimination half-lives (reported as mean ± SD) of 3.7 ± 2.7 minutes and 77.8 ± 16 minutes, respectively.

Clearance
  • Renal cl=1.7 mL/min/kg
  • Plasma cl=1.8 mL/min/kg
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirGadodiamide may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseGadodiamide may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Gadodiamide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Gadodiamide which could result in a higher serum level.
AcetaminophenGadodiamide may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Gadodiamide which could result in a higher serum level.
AclidiniumGadodiamide may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineGadodiamide may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Gadodiamide which could result in a higher serum level.
AdefovirAdefovir may decrease the excretion rate of Gadodiamide which could result in a higher serum level.
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
24847884
PubChem Substance
46504789
ChemSpider
135661
ChEBI
37333
PharmGKB
PA164784027
RxList
RxList Drug Page
Wikipedia
Gadodiamide
ATC Codes
V08CA03 — Gadodiamide
AHFS Codes
  • 92:00.00 — Miscellaneous Therapeutic Agents
MSDS
Download (56.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedDiagnosticAnatomic renal artery stenosis1
3CompletedDiagnosticAorto-Iliac Stenosis / Arterial Occlusive Diseases1
4CompletedNot AvailableChronic Kidney Disease (CKD) / Impaired Renal Function1

Pharmacoeconomics

Manufacturers
  • Ge healthcare
Packagers
  • Amersham Health Inc.
  • GE Healthcare Inc.
Dosage forms
FormRouteStrength
InjectionIntravenous287 mg/1mL
SolutionIntravenous287 mg
LiquidIntravenous287 mg
Prices
Unit descriptionCostUnit
Omniscan prefill plus syringe7.02USD ml
Omniscan 287 mg/ml vial6.98USD ml
Omniscan 287 mg/ml bottle6.49USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5560903No1996-10-012013-10-01Us
US5362475No1994-11-082011-11-08Us
CA1335819No1995-06-062012-06-06Canada

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Physiological Charge3ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area171.24 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity122.25 m3·mol-1ChemAxon
Polarizability40.72 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9808
Blood Brain Barrier+0.62
Caco-2 permeable-0.5605
P-glycoprotein substrateSubstrate0.7041
P-glycoprotein inhibitor INon-inhibitor0.9016
P-glycoprotein inhibitor IINon-inhibitor0.9571
Renal organic cation transporterNon-inhibitor0.9031
CYP450 2C9 substrateNon-substrate0.8265
CYP450 2D6 substrateNon-substrate0.8189
CYP450 3A4 substrateNon-substrate0.5872
CYP450 1A2 substrateNon-inhibitor0.9416
CYP450 2C9 inhibitorNon-inhibitor0.9189
CYP450 2D6 inhibitorNon-inhibitor0.9566
CYP450 2C19 inhibitorNon-inhibitor0.8972
CYP450 3A4 inhibitorNon-inhibitor0.9864
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9927
Ames testNon AMES toxic0.8343
CarcinogenicityNon-carcinogens0.8563
BiodegradationNot ready biodegradable0.7604
Rat acute toxicity1.9159 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9582
hERG inhibition (predictor II)Non-inhibitor0.9424
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
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 acid amides
Alternative Parents
Alpha amino acids / Tricarboxylic acids and derivatives / Trialkylamines / Secondary carboxylic acid amides / Carboxylic acid salts / Amino acids / Carboxylic acids / Organopnictogen compounds / Organic zwitterions / Organic salts
show 3 more
Substituents
Alpha-amino acid amide / Alpha-amino acid / Tricarboxylic acid or derivatives / Carboxamide group / Carboxylic acid salt / Secondary carboxylic acid amide / Tertiary amine / Tertiary aliphatic amine / Amino acid / Carboxylic acid
show 12 more
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
gadolinium coordination entity (CHEBI:37333)

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 13:32