You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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.

Structure
Thumb
Synonyms
Ibutilid
Ibutilida
Ibutilide
Ibutilidum
N-(4-{4-[ethyl(heptyl)amino]-1-hydroxybutyl}phenyl)methanesulfonamide
External Identifiers
  • U 70226 E
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Corvertinjection, solution.1 mg/mLintravenousPharmacia and Upjohn Company1995-12-28Not applicableUs
Corvert Injectionsolution0.1 mgintravenousPfizer Canada Inc2000-11-28Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ibutilide Fumarateinjection, solution.1 mg/mLintravenousGenera Medix Inc.2010-01-12Not applicableUs
Ibutilide Fumarateinjection, solution.1 mg/mLintravenousMylan Institutional LLC2010-01-11Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Ibutilide fumarate
122647-32-9
ThumbNot applicableDBSALT001069
Categories
UNII2436VX1U9B
CAS number122647-31-8
WeightAverage: 384.576
Monoisotopic: 384.244663718
Chemical FormulaC20H36N2O3S
InChI KeyInChIKey=ALOBUEHUHMBRLE-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
Related Articles
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 inhibitorNon-inhibitor0.8256
CYP450 2D6 inhibitorNon-inhibitor0.8114
CYP450 2C19 inhibitorNon-inhibitor0.7115
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
  • Bioniche pharma usa llc
  • Pharmaforce inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionintravenous.1 mg/mL
Solutionintravenous0.1 mg
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
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5155268 No1992-12-282009-12-28Us
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 ReferencesNot Available
External Links
ATC CodesC01BD05
AHFS Codes
  • 24:04.04.20
PDB EntriesNot Available
FDA labelDownload (878 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
CitalopramCitalopram may increase the QTc-prolonging activities of Ibutilide.
DofetilideDofetilide may increase the QTc-prolonging activities of Ibutilide.
FingolimodFingolimod may increase the arrhythmogenic activities of Ibutilide.
GoserelinGoserelin may increase the QTc-prolonging activities of Ibutilide.
IvabradineIvabradine may increase the QTc-prolonging activities of Ibutilide.
LeuprolideLeuprolide may increase the QTc-prolonging activities of Ibutilide.
LidocaineLidocaine may increase the arrhythmogenic activities of Ibutilide.
MifepristoneMifepristone may increase the QTc-prolonging activities of Ibutilide.
OctreotideOctreotide may increase the QTc-prolonging activities of Ibutilide.
PropafenonePropafenone may increase the arrhythmogenic activities of Ibutilide.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
activator
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belon...
Gene Name:
CACNA1C
Uniprot ID:
Q13936
Molecular Weight:
248974.1 Da
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:15926871 ]
  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:9257085 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
activator
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB1
Uniprot ID:
Q02641
Molecular Weight:
65712.995 Da
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:15926871 ]
  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:9257085 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are r...
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
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:15266014 ]
  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:16291873 ]
  3. Wolpert C, Schimpf R, Veltmann C, Borggrefe M: [Short QT syndrome]. Herz. 2007 May;32(3):206-10. [PubMed:17497253 ]
  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:16076272 ]
  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:11602820 ]
  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:15926871 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
activator
General Function:
Voltage-gated calcium channel activity
Specific Function:
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling (By similarity).
Gene Name:
CACNA2D1
Uniprot ID:
P54289
Molecular Weight:
124566.93 Da
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:15926871 ]
  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:9257085 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
activator
General Function:
Voltage-gated calcium channel activity
Specific Function:
This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex.
Gene Name:
CACNG1
Uniprot ID:
Q06432
Molecular Weight:
25028.105 Da
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:15926871 ]
  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:9257085 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium channel activity
Specific Function:
Ion channel that contributes to passive transmembrane potassium transport and to the regulation of the resting membrane potential in brain astrocytes, but also in kidney and in other tissues (PubMed:15820677, PubMed:21653227). Forms dimeric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel is selective for K(+) ions at physiological potass...
Gene Name:
KCNK1
Uniprot ID:
O00180
Molecular Weight:
38142.775 Da
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:15926871 ]
  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:9257085 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Potassium ion leak channel activity
Specific Function:
Exhibits outward rectification in a physiological K(+) gradient and mild inward rectification in symmetrical K(+) conditions.
Gene Name:
KCNK6
Uniprot ID:
Q9Y257
Molecular Weight:
33746.8 Da
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:15926871 ]
  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:9257085 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Voltage-gated potassium channel activity
Specific Function:
Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current (By similarity). Channel properties may be modulated by cAMP and subunit assembly.
Gene Name:
KCNH6
Uniprot ID:
Q9H252
Molecular Weight:
109923.705 Da
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:15926871 ]
  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:9257085 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Voltage-gated potassium channel activity
Specific Function:
Pore-forming (alpha) subunit of voltage-gated potassium channel. Channel properties may be modulated by cAMP and subunit assembly.
Gene Name:
KCNH7
Uniprot ID:
Q9NS40
Molecular Weight:
134998.525 Da
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:15926871 ]
  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:9257085 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Voltage-gated potassium channel activity
Specific Function:
This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectific...
Gene Name:
KCNJ11
Uniprot ID:
Q14654
Molecular Weight:
43540.375 Da
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:15926871 ]
  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:9257085 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on April 28, 2016 21:16