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Identification
NameIbutilide
Accession NumberDB00308  (APRD01025)
TypeSmall Molecule
GroupsApproved
Description

Ibutilide is a Class III antiarrhythmic agent that is indicated for acute cardioconversion of atrial fibrillation and atrial flutter of a recent onset to sinus rhythm. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
CorvertNot AvailableNot Available
IbutilidGermanINN
IbutilidaSpanishINN
IbutilideNot AvailableBAN
Ibutilide FumarateNot AvailableNot Available
IbutilidumLatinINN
N-(4-{4-[ethyl(heptyl)amino]-1-hydroxybutyl}phenyl)methanesulfonamideNot AvailableIUPAC
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Corvertinjection, solution.1 mg/mLintravenousPharmacia and Upjohn Company1995-12-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Corvertinjection, solution.1 mg/mLintravenousPharmacia and Upjohn Company1995-12-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Corvertinjection, solution.1 mg/mLintravenousPharmacia and Upjohn Company1995-12-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ibutilide Fumarateinjection, solution.1 mg/mLintravenousPaddock Laboratories, Inc.2010-01-13Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Ibutilide Fumarateinjection, solution.1 mg/mLintravenousGenera Medix Inc.2010-01-12Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Ibutilide Fumarateinjection, solution.1 mg/mLintravenousMylan Institutional LLC2013-01-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Ibutilide Fumarate
ThumbNot applicableDBSALT001069
Categories
CAS number122647-32-9
WeightAverage: 384.576
Monoisotopic: 384.244663718
Chemical FormulaC20H36N2O3S
InChI KeyALOBUEHUHMBRLE-UHFFFAOYSA-N
InChI
InChI=1S/C20H36N2O3S/c1-4-6-7-8-9-16-22(5-2)17-10-11-20(23)18-12-14-19(15-13-18)21-26(3,24)25/h12-15,20-21,23H,4-11,16-17H2,1-3H3
IUPAC Name
N-(4-{4-[ethyl(heptyl)amino]-1-hydroxybutyl}phenyl)methanesulfonamide
SMILES
CCCCCCCN(CC)CCCC(O)C1=CC=C(NS(C)(=O)=O)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylbutylamines. These are compounds containing a phenylbutylamine moiety, which consists of a phenyl group substituted at the fourth carbon by an butan-1-amine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylbutylamines
Direct ParentPhenylbutylamines
Alternative Parents
Substituents
  • Phenylbutylamine
  • Sulfanilide
  • Aralkylamine
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Hydrocarbon derivative
  • Aromatic alcohol
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationIndicated for the rapid conversion of atrial fibrillation or atrial flutter of recent onset to sinus rhythm.
PharmacodynamicsIbutilide prolongs the action potential duration and increases both atrial and ventricular refractoriness in vivo, i.e., class III electrophysiologic effects. Voltage clamp studies indicate that ibutilide, at nanomolar concentrations, delays repolarization by activation of a slow, inward current (predominantly sodium), rather than by blocking outward potassium currents, which is the mechanism by which most other class III antiarrhythmics act.
Mechanism of actionIbutilide is a 'pure' class III antiarrhythmic drug, used intravenously against atrial flutter and fibrillation. At a cellular level it exerts two main actions: induction of a persistent Na+ current sensitive to dihydropyridine Ca2+ channel blockers and potent inhibition of the cardiac rapid delayed rectifier K+ current, by binding within potassium channel pores. In other words, Ibutilide binds to and alters the activity of hERG potassium channels, delayed inward rectifier potassium (IKr) channels and L-type (dihydropyridine sensitive) calcium channels
AbsorptionRapid after intravenous injection
Volume of distribution
  • 11 L/kg
Protein binding40%
Metabolism

Primarily hepatic. Eight metabolites of ibutilide were detected in metabolic profiling of urine. These metabolites are thought to be formed primarily by o-oxidation followed by sequential b-oxidation of the heptyl side chain of ibutilide. Of the eight metabolites, only the o-hydroxy metabolite possesses class III electrophysiologic properties similar to that of ibutilide in an in vitro isolated rabbit myocardium model.

Route of eliminationIn healthy male volunteers, about 82% of a 0.01 mg/kg dose of [14C] ibutilide fumarate was excreted in the urine (about 7% of the dose as unchanged ibutilide) and the remainder (about 19%) was recovered in the feces.
Half life6 hours (ranges from 2-12 hours)
Clearance
  • 29 mL/min/kg
ToxicityAcute overdose in animals results in CNS toxicity; notably, CNS depression, rapid gasping breathing, and convulsions. The intravenous median lethal dose in the rat was more than 50 mg/kg which is, on a mg/m2 basis, at least 250 times the maximum recommended human dose.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Ibutilide Action PathwayDrug actionSMP00332
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9964
Blood Brain Barrier+0.9363
Caco-2 permeable-0.6669
P-glycoprotein substrateSubstrate0.6142
P-glycoprotein inhibitor INon-inhibitor0.7689
P-glycoprotein inhibitor IINon-inhibitor0.8893
Renal organic cation transporterNon-inhibitor0.8738
CYP450 2C9 substrateNon-substrate0.8131
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5472
CYP450 1A2 substrateNon-inhibitor0.7721
CYP450 2C9 substrateNon-inhibitor0.8256
CYP450 2D6 substrateNon-inhibitor0.8114
CYP450 2C19 substrateNon-inhibitor0.7115
CYP450 3A4 substrateNon-inhibitor0.7974
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8467
Ames testNon AMES toxic0.7092
CarcinogenicityNon-carcinogens0.6799
BiodegradationNot ready biodegradable0.9945
Rat acute toxicity2.5314 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5736
hERG inhibition (predictor II)Inhibitor0.7592
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
  • Bioniche pharma usa llc
  • Pharmaforce inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionintravenous.1 mg/mL
Prices
Unit descriptionCostUnit
Corvert 1 mg/10 ml vial54.27USD ml
Ibutilide fum 1 mg/10 ml vial33.6USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States51552681992-12-282009-12-28
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubility100 mg/mLNot Available
logP4.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00473 mg/mLALOGPS
logP4.72ALOGPS
logP2.54ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)9.72ChemAxon
pKa (Strongest Basic)10.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area69.64 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity109.18 m3·mol-1ChemAxon
Polarizability46.45 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US5155268A
General ReferenceNot Available
External Links
ATC CodesC01BD05
AHFS Codes
  • 24:04.04.20
PDB EntriesNot Available
FDA labelDownload (878 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
FingolimodMay enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class III).
MifepristoneMay enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents.
PropafenoneMay enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class III).
Food InteractionsNot Available

Targets

1. Voltage-dependent L-type calcium channel subunit alpha-1C

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: activator

Components

Name UniProt ID Details
Voltage-dependent L-type calcium channel subunit alpha-1C Q13936 Details

References:

  1. Doggrell SA, Hancox JC: Ibutilide—recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. Pubmed
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Voltage-dependent L-type calcium channel subunit beta-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: activator

Components

Name UniProt ID Details
Voltage-dependent L-type calcium channel subunit beta-1 Q02641 Details

References:

  1. Doggrell SA, Hancox JC: Ibutilide—recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. Pubmed
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. Pubmed

3. Potassium voltage-gated channel subfamily H member 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily H member 2 Q12809 Details

References:

  1. Perry M, de Groot MJ, Helliwell R, Leishman D, Tristani-Firouzi M, Sanguinetti MC, Mitcheson J: Structural determinants of HERG channel block by clofilium and ibutilide. Mol Pharmacol. 2004 Aug;66(2):240-9. Pubmed
  2. Perry M, Stansfeld PJ, Leaney J, Wood C, de Groot MJ, Leishman D, Sutcliffe MJ, Mitcheson JS: Drug binding interactions in the inner cavity of HERG channels: molecular insights from structure-activity relationships of clofilium and ibutilide analogs. Mol Pharmacol. 2006 Feb;69(2):509-19. Epub 2005 Nov 16. Pubmed
  3. Wolpert C, Schimpf R, Veltmann C, Borggrefe M: [Short QT syndrome] Herz. 2007 May;32(3):206-10. Pubmed
  4. Wolpert C, Schimpf R, Veltmann C, Giustetto C, Gaita F, Borggrefe M: Clinical characteristics and treatment of short QT syndrome. Expert Rev Cardiovasc Ther. 2005 Jul;3(4):611-7. Pubmed
  5. Yang T, Snyders D, Roden DM: Drug block of I(kr): model systems and relevance to human arrhythmias. J Cardiovasc Pharmacol. 2001 Nov;38(5):737-44. Pubmed
  6. Doggrell SA, Hancox JC: Ibutilide—recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. Pubmed

4. Voltage-dependent calcium channel subunit alpha-2/delta-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: activator

Components

Name UniProt ID Details
Voltage-dependent calcium channel subunit alpha-2/delta-1 P54289 Details

References:

  1. Doggrell SA, Hancox JC: Ibutilide—recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. Pubmed
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. Pubmed

5. Voltage-dependent calcium channel gamma-1 subunit

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: activator

Components

Name UniProt ID Details
Voltage-dependent calcium channel gamma-1 subunit Q06432 Details

References:

  1. Doggrell SA, Hancox JC: Ibutilide—recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. Pubmed
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. Pubmed

6. Potassium channel subfamily K member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Potassium channel subfamily K member 1 O00180 Details

References:

  1. Doggrell SA, Hancox JC: Ibutilide—recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. Pubmed
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. Pubmed

7. Potassium channel subfamily K member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Potassium channel subfamily K member 6 Q9Y257 Details

References:

  1. Doggrell SA, Hancox JC: Ibutilide—recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. Pubmed
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. Pubmed

8. Potassium voltage-gated channel subfamily H member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily H member 6 Q9H252 Details

References:

  1. Doggrell SA, Hancox JC: Ibutilide—recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. Pubmed
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. Pubmed

9. Potassium voltage-gated channel subfamily H member 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily H member 7 Q9NS40 Details

References:

  1. Doggrell SA, Hancox JC: Ibutilide—recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. Pubmed
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. Pubmed

10. ATP-sensitive inward rectifier potassium channel 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
ATP-sensitive inward rectifier potassium channel 11 Q14654 Details

References:

  1. Doggrell SA, Hancox JC: Ibutilide—recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. Pubmed
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on March 24, 2014 11:11