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Identification
NameDronedarone
Accession NumberDB04855
TypeSmall Molecule
GroupsApproved
Description

Dronedarone is a sinus rhythm controller for management of paroxysmal or persistent atrial fibrillation. Classified as a Class III antiarrhythmic but displays properties of all four Vaughan-Williams classes, dronedarone blocks a multitude of channels (sodium, potassium, calcium), and demonstrates antiadrenergic properties. Chemically, it is a benzofuran derivative. FDA approved on July 1, 2009.

Structure
Thumb
Synonyms
Multaq
N-(2-Butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)-5-benzofuranyl)-methanesulfonamide
N-(2-Butyl-3-(P-(3-(dibutylamino)propoxy)benzoyl)-5-benzofuranyl)methanesulfonamide
SR 33589
SR 33589b
External Identifiers
  • SR33589
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Multaqtablet, film coated400 mg/1oralSanofi Aventis U.S. Llc2009-07-01Not applicableUs
Multaqtablet400 mgoralSanofi Aventis Canada Inc2009-09-28Not applicableCanada
Multaqtablet, film coated400 mg/1oralCardinal Health2009-07-01Not applicableUs
Multaqtablet, film coated400 mg/1oralPhysicians Total Care, Inc.2010-02-23Not applicableUs
Multaqtablet, film coated400 mg/1oralSanofi Winthrop Industries2009-07-01Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Dronedarone Hydrochloride
Thumb
  • InChI Key: DWKVCQXJYURSIQ-UHFFFAOYSA-N
  • Monoisotopic Mass: 592.273770957
  • Average Mass: 593.217
DBSALT000061
Categories
UNIIJQZ1L091Y2
CAS number141626-36-0
WeightAverage: 556.756
Monoisotopic: 556.297093218
Chemical FormulaC31H44N2O5S
InChI KeyInChIKey=ZQTNQVWKHCQYLQ-UHFFFAOYSA-N
InChI
InChI=1S/C31H44N2O5S/c1-5-8-12-29-30(27-23-25(32-39(4,35)36)15-18-28(27)38-29)31(34)24-13-16-26(17-14-24)37-22-11-21-33(19-9-6-2)20-10-7-3/h13-18,23,32H,5-12,19-22H2,1-4H3
IUPAC Name
N-(2-butyl-3-{4-[3-(dibutylamino)propoxy]benzoyl}-1-benzofuran-5-yl)methanesulfonamide
SMILES
CCCCN(CCCC)CCCOC1=CC=C(C=C1)C(=O)C1=C(CCCC)OC2=C1C=C(NS(C)(=O)=O)C=C2
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as sulfanilides. These are organic aromatic compounds containing a sulfanilide moiety, with the general structure RS(=O)(=O)NC1=CC=CC=C1.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassSulfanilides
Direct ParentSulfanilides
Alternative Parents
Substituents
  • Sulfanilide
  • Benzofuran
  • Acetophenone
  • Aryl ketone
  • 3-aroylfuran
  • Phenol ether
  • Benzoyl
  • Alkyl aryl ether
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Furan
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ketone
  • Oxacycle
  • Organoheterocyclic compound
  • Ether
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationManagement of paroxysmal or persistent atrial fibrillation via restoration of normal sinus rhythm.
PharmacodynamicsDronedarone is a non-iodinated benzofuran derivative for the management of paroxysmal or persistent atrial fibrillation. Dronedarone inhibits human atrial sodium currents (INa) in a dose dependent manner in which a concentration of 0.3 μM is sufficient to completely inhibit INa. Chemically it is related to amiodarone, a popular antiarrhythmic the use of which is limited to toxicity due its high iodine content (pulmonary fibrosis, thyroid disease) as well as by liver disease. Dronedarone lacks the iodine, and is expected to have less toxicity, yet it displays amiodarone-like class III antiarrhytmic activity in vitro and in clinical trials. Despite this advantage over amiodarone, clinical trials of dronedarone have shown that it may increase risk of stroke and mortality from cardiovascular causes and arrhythmia. Furthermore, amiodarone more potently effects action potential and refractory periods than dronedarone.
Mechanism of actionThe antiarrhythmic effect of dronedarone may be due to at least two major actions. It prolongs the duration of action potential and refractory period in myocardial tissue via inhibition of sodium and potassium channels. Via inhibition of calcium channels and blockage of beta1-adrenergic receptors, a decrease in AV conduction and sinus node function can be observed. Dronedarone can also cause an increase in blood pressure by inhibition of alpha1-adrenergic receptors.
Related Articles
AbsorptionBecause of presystemic first pass metabolism the absolute bioavailability of dronedarone without food is low, about 4%. It increases to approximately 15% when dronedarone is administered with a high fat meal. After oral administration in fed conditions, peak plasma concentrations of dronedarone and the main circulating active metabolite (N-debutyl metabolite) are reached within 3 to 6 hours. After repeated administration of 400 mg twice daily, steady state is reached within 4 to 8 days of treatment. The steady state Cmax and exposure of the main N-debutyl metabolite is similar to that of the parent compound.
Volume of distribution

When intravenously administered, the volume of distribution is 1400 L.

Protein bindingDronedarone and its N-debutyl metabolite is >98% protein bound - mainly to albumin.
Metabolism

Majority of dronedarone is eliminated by first-pass metabolism in the liver by CYP3A4 enzymes (>84%). Dronedarone is also metabolized by CYP2D6 to a lesser extent. N-DBD is its active metabolite (1/10 to 1/3 potency of dronedarone) which can penetrate the blood-brain barrier, placenta, and is excreted in breast milk. However, it does not significantly accumulate in plasma or tissue.

Route of elimination6% of the dose was excreted in the urine, mainly as metabolites (no unchanged compound excreted in urine), and 84% was excreted in feces, mainly as metabolites.
Half lifeElimination half-life: 13-19 hours
Clearance

Plasma clearance = 130-150 L/h.

ToxicityMost common adverse reactions (≥2%) are diarrhea, nausea, abdominal pain, vomiting, and asthenia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9156
Caco-2 permeable-0.6057
P-glycoprotein substrateSubstrate0.6265
P-glycoprotein inhibitor IInhibitor0.7879
P-glycoprotein inhibitor IINon-inhibitor0.5218
Renal organic cation transporterNon-inhibitor0.7334
CYP450 2C9 substrateNon-substrate0.7339
CYP450 2D6 substrateNon-substrate0.7682
CYP450 3A4 substrateSubstrate0.6963
CYP450 1A2 substrateNon-inhibitor0.5487
CYP450 2C9 inhibitorInhibitor0.6209
CYP450 2D6 inhibitorNon-inhibitor0.8299
CYP450 2C19 inhibitorNon-inhibitor0.5319
CYP450 3A4 inhibitorNon-inhibitor0.5198
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8288
Ames testNon AMES toxic0.5248
CarcinogenicityNon-carcinogens0.6132
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6273 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.8036
hERG inhibition (predictor II)Inhibitor0.8051
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral400 mg
Tablet, film coatedoral400 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2047773 No2000-09-122011-07-24Canada
CA2294812 No2009-09-292018-06-19Canada
US5223510 No1996-07-262016-07-26Us
US7323493 No1998-06-192018-06-19Us
US8318800 No1998-06-192018-06-19Us
US8410167 No2009-04-162029-04-16Us
US8602215 No2011-06-302031-06-30Us
US9107900 No2009-04-162029-04-16Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityInsoluble FDA label
logP7.346MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.00201 mg/mLALOGPS
logP6.46ALOGPS
logP5.28ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)9.08ChemAxon
pKa (Strongest Basic)9.79ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area88.85 Å2ChemAxon
Rotatable Bond Count17ChemAxon
Refractivity158.13 m3·mol-1ChemAxon
Polarizability66.05 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Arie Gutman, Gennadi Nisnevich, Lev Yudovitch, “Process for the preparation of dronedarone.” U.S. Patent US20050049302, issued March 03, 2005.

US20050049302
General References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667 ]
  2. Iwamoto T, Watanabe Y, Kita S, Blaustein MP: Na+/Ca2+ exchange inhibitors: a new class of calcium regulators. Cardiovasc Hematol Disord Drug Targets. 2007 Sep;7(3):188-98. [PubMed:17896959 ]
  3. Celestino D, Medei E, Moro S, Elizari MV, Sicouri S: Acute in vitro effects of dronedarone, an iodine-free derivative, and amiodarone, on the rabbit sinoatrial node automaticity: a comparative study. J Cardiovasc Pharmacol Ther. 2007 Sep;12(3):248-57. [PubMed:17875953 ]
  4. Pamukcu B, Lip GY: Dronedarone as a new treatment option for atrial fibrillation patients: pharmacokinetics, pharmacodynamics and clinical practice. Expert Opin Pharmacother. 2011 Jan;12(1):131-40. doi: 10.1517/14656566.2011.540800. Epub 2010 Dec 2. [PubMed:21126199 ]
  5. De Ferrari GM, Dusi V: Drug safety evaluation of dronedarone in atrial fibrillation. Expert Opin Drug Saf. 2012 Nov;11(6):1023-45. doi: 10.1517/14740338.2012.722994. Epub 2012 Sep 13. [PubMed:22971242 ]
External Links
ATC CodesC01BD07
AHFS Codes
  • 24:04.04.20
PDB EntriesNot Available
FDA labelDownload (606 KB)
MSDSDownload (115 KB)
Interactions
Drug Interactions
Drug
AcebutololDronedarone may increase the bradycardic activities of Acebutolol.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Dronedarone.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Dronedarone.
ApixabanThe serum concentration of Apixaban can be increased when it is combined with Dronedarone.
AprepitantThe serum concentration of Dronedarone can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Dronedarone can be increased when it is combined with Atazanavir.
AtenololDronedarone may increase the bradycardic activities of Atenolol.
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Dronedarone.
AvanafilThe serum concentration of Avanafil can be increased when it is combined with Dronedarone.
BetaxololDronedarone may increase the bradycardic activities of Betaxolol.
BexaroteneThe serum concentration of Dronedarone can be decreased when it is combined with Bexarotene.
BisoprololDronedarone may increase the bradycardic activities of Bisoprolol.
BoceprevirThe serum concentration of Dronedarone can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Dronedarone can be decreased when it is combined with Bosentan.
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Dronedarone.
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Dronedarone.
BretyliumBretylium may increase the bradycardic activities of Dronedarone.
BrexpiprazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Dronedarone.
BudesonideThe serum concentration of Budesonide can be increased when it is combined with Dronedarone.
CarbamazepineThe serum concentration of Dronedarone can be decreased when it is combined with Carbamazepine.
CarteololDronedarone may increase the bradycardic activities of Carteolol.
CarvedilolDronedarone may increase the bradycardic activities of Carvedilol.
CeritinibDronedarone may increase the bradycardic activities of Ceritinib.
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Dronedarone.
CitalopramCitalopram may increase the QTc-prolonging activities of Dronedarone.
ClarithromycinThe serum concentration of Dronedarone can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Dronedarone can be increased when it is combined with Cobicistat.
CodeineThe therapeutic efficacy of Codeine can be decreased when used in combination with Dronedarone.
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Dronedarone.
ConivaptanThe serum concentration of Dronedarone can be increased when it is combined with Conivaptan.
CyclosporineThe serum concentration of Dronedarone can be increased when it is combined with Cyclosporine.
Dabigatran etexilateThe serum concentration of Dabigatran etexilate can be increased when it is combined with Dronedarone.
DabrafenibThe serum concentration of Dronedarone can be decreased when it is combined with Dabrafenib.
DapoxetineThe serum concentration of Dapoxetine can be increased when it is combined with Dronedarone.
DarunavirThe serum concentration of Dronedarone can be increased when it is combined with Darunavir.
DeferasiroxThe serum concentration of Dronedarone can be decreased when it is combined with Deferasirox.
DicoumarolThe serum concentration of Dicoumarol can be increased when it is combined with Dronedarone.
DigoxinDigoxin may increase the atrioventricular blocking (AV block) activities of Dronedarone.
DiltiazemDiltiazem may increase the atrioventricular blocking (AV block) activities of Dronedarone.
DocetaxelThe serum concentration of Docetaxel can be increased when it is combined with Dronedarone.
DofetilideDofetilide may increase the QTc-prolonging activities of Dronedarone.
DomperidoneThe serum concentration of Domperidone can be increased when it is combined with Dronedarone.
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Dronedarone.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Dronedarone.
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Dronedarone.
EletriptanThe serum concentration of Eletriptan can be increased when it is combined with Dronedarone.
EnzalutamideThe serum concentration of Dronedarone can be decreased when it is combined with Enzalutamide.
EplerenoneThe serum concentration of Eplerenone can be increased when it is combined with Dronedarone.
EsmololDronedarone may increase the bradycardic activities of Esmolol.
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Dronedarone.
FentanylThe serum concentration of Fentanyl can be increased when it is combined with Dronedarone.
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Dronedarone.
FingolimodFingolimod may increase the arrhythmogenic activities of Dronedarone.
FlibanserinThe serum concentration of Flibanserin can be increased when it is combined with Dronedarone.
FluconazoleThe metabolism of Dronedarone can be decreased when combined with Fluconazole.
FlunisolideThe metabolism of Flunisolide can be decreased when combined with Dronedarone.
FluvoxamineThe metabolism of Fluvoxamine can be decreased when combined with Dronedarone.
FosaprepitantThe serum concentration of Dronedarone can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Dronedarone can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Dronedarone can be increased when it is combined with Fusidic Acid.
GoserelinGoserelin may increase the QTc-prolonging activities of Dronedarone.
HydrocodoneThe serum concentration of Hydrocodone can be increased when it is combined with Dronedarone.
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Dronedarone.
IdelalisibThe serum concentration of Dronedarone can be increased when it is combined with Idelalisib.
IfosfamideThe serum concentration of the active metabolites of Ifosfamide can be reduced when Ifosfamide is used in combination with Dronedarone resulting in a loss in efficacy.
ImatinibThe serum concentration of Imatinib can be increased when it is combined with Dronedarone.
IndinavirThe serum concentration of Dronedarone can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Dronedarone can be increased when it is combined with Itraconazole.
IvabradineThe serum concentration of Ivabradine can be increased when it is combined with Dronedarone.
IvacaftorThe serum concentration of Ivacaftor can be increased when it is combined with Dronedarone.
KetoconazoleThe serum concentration of Dronedarone can be increased when it is combined with Ketoconazole.
LabetalolDronedarone may increase the bradycardic activities of Labetalol.
LacosamideDronedarone may increase the atrioventricular blocking (AV block) activities of Lacosamide.
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Dronedarone.
LeuprolideLeuprolide may increase the QTc-prolonging activities of Dronedarone.
LevobunololDronedarone may increase the bradycardic activities of Levobunolol.
LidocaineLidocaine may increase the arrhythmogenic activities of Dronedarone.
LomitapideThe serum concentration of Lomitapide can be increased when it is combined with Dronedarone.
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Dronedarone.
LuliconazoleThe serum concentration of Dronedarone can be increased when it is combined with Luliconazole.
LurasidoneThe serum concentration of Lurasidone can be increased when it is combined with Dronedarone.
MetipranololDronedarone may increase the bradycardic activities of Metipranolol.
MetoprololDronedarone may increase the bradycardic activities of Metoprolol.
MifepristoneMifepristone may increase the QTc-prolonging activities of Dronedarone.
MitotaneThe serum concentration of Dronedarone can be decreased when it is combined with Mitotane.
NadololDronedarone may increase the bradycardic activities of Nadolol.
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Dronedarone.
NebivololDronedarone may increase the bradycardic activities of Nebivolol.
NefazodoneThe serum concentration of Dronedarone can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Dronedarone can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Dronedarone can be increased when it is combined with Netupitant.
NimodipineThe serum concentration of Nimodipine can be increased when it is combined with Dronedarone.
NintedanibThe serum concentration of Nintedanib can be increased when it is combined with Dronedarone.
OctreotideOctreotide may increase the bradycardic activities of Dronedarone.
OlaparibThe serum concentration of Olaparib can be increased when it is combined with Dronedarone.
OxycodoneThe risk or severity of adverse effects can be increased when Dronedarone is combined with Oxycodone.
PalbociclibThe serum concentration of Dronedarone can be increased when it is combined with Palbociclib.
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Dronedarone.
PenbutololDronedarone may increase the bradycardic activities of Penbutolol.
PhenobarbitalThe serum concentration of Dronedarone can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Dronedarone can be decreased when it is combined with Phenytoin.
PimecrolimusThe metabolism of Pimecrolimus can be decreased when combined with Dronedarone.
PimozideThe serum concentration of Pimozide can be increased when it is combined with Dronedarone.
PindololDronedarone may increase the bradycardic activities of Pindolol.
PosaconazoleThe serum concentration of Dronedarone can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Dronedarone can be decreased when it is combined with Primidone.
PropafenonePropafenone may increase the arrhythmogenic activities of Dronedarone.
PropranololDronedarone may increase the bradycardic activities of Propranolol.
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Dronedarone.
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Dronedarone.
RifabutinThe serum concentration of Dronedarone can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Dronedarone can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Dronedarone can be decreased when it is combined with Rifapentine.
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Dronedarone.
RitonavirThe serum concentration of Dronedarone can be increased when it is combined with Ritonavir.
RivaroxabanThe serum concentration of Rivaroxaban can be increased when it is combined with Dronedarone.
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Dronedarone.
RuxolitinibRuxolitinib may increase the bradycardic activities of Dronedarone.
SaquinavirThe serum concentration of Dronedarone can be increased when it is combined with Saquinavir.
SaxagliptinThe serum concentration of Saxagliptin can be increased when it is combined with Dronedarone.
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Dronedarone.
SiltuximabThe serum concentration of Dronedarone can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Simeprevir can be increased when it is combined with Dronedarone.
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Dronedarone.
SonidegibThe serum concentration of Sonidegib can be increased when it is combined with Dronedarone.
St. John's WortThe serum concentration of Dronedarone can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Dronedarone can be increased when it is combined with Stiripentol.
SuvorexantThe serum concentration of Suvorexant can be increased when it is combined with Dronedarone.
TacrolimusTacrolimus may increase the QTc-prolonging activities of Dronedarone.
TamoxifenThe serum concentration of the active metabolites of Tamoxifen can be reduced when Tamoxifen is used in combination with Dronedarone resulting in a loss in efficacy.
TelaprevirThe serum concentration of Dronedarone can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Dronedarone can be increased when it is combined with Telithromycin.
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Dronedarone.
TimololDronedarone may increase the bradycardic activities of Timolol.
TocilizumabThe serum concentration of Dronedarone can be decreased when it is combined with Tocilizumab.
TofacitinibTofacitinib may increase the bradycardic activities of Dronedarone.
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Dronedarone.
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Dronedarone.
TrabectedinThe serum concentration of Trabectedin can be increased when it is combined with Dronedarone.
TramadolThe therapeutic efficacy of Tramadol can be decreased when used in combination with Dronedarone.
UlipristalThe serum concentration of Ulipristal can be increased when it is combined with Dronedarone.
VerapamilVerapamil may increase the atrioventricular blocking (AV block) activities of Dronedarone.
VilazodoneThe serum concentration of Vilazodone can be increased when it is combined with Dronedarone.
VincristineThe serum concentration of Vincristine can be increased when it is combined with Dronedarone.
VindesineThe serum concentration of Vindesine can be increased when it is combined with Dronedarone.
VoriconazoleThe serum concentration of Dronedarone can be increased when it is combined with Voriconazole.
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Dronedarone.
ZopicloneThe serum concentration of Zopiclone can be increased when it is combined with Dronedarone.
Food Interactions
  • Absorption of dronedarone increases 3-fold if taken with food especially if meal is high in fat content
  • Do not take dronedarone with grapefruit juice. Grapefruit juice is a potent CYP3A4 inhibitor which will increase serum concentrations of dronedarone threefold

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Alpha1-adrenergic receptor activity
Specific Function:
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name:
ADRA1D
Uniprot ID:
P25100
Molecular Weight:
60462.205 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Thioesterase binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianser...
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Epinephrine binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phent...
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Protein homodimerization activity
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name:
ADRA2C
Uniprot ID:
P18825
Molecular Weight:
49521.585 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Receptor signaling protein activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular Weight:
51322.1 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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. Iwamoto T, Watanabe Y, Kita S, Blaustein MP: Na+/Ca2+ exchange inhibitors: a new class of calcium regulators. Cardiovasc Hematol Disord Drug Targets. 2007 Sep;7(3):188-98. [PubMed:17896959 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated calcium channel activity involved sa node cell action potential
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-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belon...
Gene Name:
CACNA1D
Uniprot ID:
Q01668
Molecular Weight:
245138.75 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
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-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belon...
Gene Name:
CACNA1F
Uniprot ID:
O60840
Molecular Weight:
220675.9 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
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-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belon...
Gene Name:
CACNA1S
Uniprot ID:
Q13698
Molecular Weight:
212348.1 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
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
Kind
Protein
Organism
Human
Pharmacological action
unknown
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:
CACNB2
Uniprot ID:
Q08289
Molecular Weight:
73579.925 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
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:
CACNB3
Uniprot ID:
P54284
Molecular Weight:
54531.425 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
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:
CACNB4
Uniprot ID:
O00305
Molecular Weight:
58168.625 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN1A
Uniprot ID:
P35498
Molecular Weight:
228969.49 Da
References
  1. Lalevee N, Nargeot J, Barrere-Lemaire S, Gautier P, Richard S: Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes. J Cardiovasc Electrophysiol. 2003 Aug;14(8):885-90. [PubMed:12890054 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Potassium ion leak channel activity
Specific Function:
Ion channel that contributes to passive transmembrane potassium transport (PubMed:23169818). Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward rectifying potassium channel in a phosphorylation-dependent manner (PubMed:11319556). In astrocytes, forms mostly heterodimeric potassium channels with KCNK1, with only a minor proportion of function...
Gene Name:
KCNK2
Uniprot ID:
O95069
Molecular Weight:
47092.215 Da
References
  1. Schmidt C, Wiedmann F, Schweizer PA, Becker R, Katus HA, Thomas D: Novel electrophysiological properties of dronedarone: inhibition of human cardiac two-pore-domain potassium (K2P) channels. Naunyn Schmiedebergs Arch Pharmacol. 2012 Oct;385(10):1003-16. doi: 10.1007/s00210-012-0780-9. Epub 2012 Jul 13. [PubMed:22790794 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Schafer JA, Kjesbo NK, Gleason PP: Dronedarone: current evidence and future questions. Cardiovasc Ther. 2010 Spring;28(1):38-47. doi: 10.1111/j.1755-5922.2009.00112.x. [PubMed:20074258 ]
  2. De Ferrari GM, Dusi V: Drug safety evaluation of dronedarone in atrial fibrillation. Expert Opin Drug Saf. 2012 Nov;11(6):1023-45. doi: 10.1517/14740338.2012.722994. Epub 2012 Sep 13. [PubMed:22971242 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Dorian P: Clinical pharmacology of dronedarone: implications for the therapy of atrial fibrillation. J Cardiovasc Pharmacol Ther. 2010 Dec;15(4 Suppl):15S-8S. doi: 10.1177/1074248410367792. Epub 2010 May 14. [PubMed:20472816 ]
  2. Schafer JA, Kjesbo NK, Gleason PP: Dronedarone: current evidence and future questions. Cardiovasc Ther. 2010 Spring;28(1):38-47. doi: 10.1111/j.1755-5922.2009.00112.x. [PubMed:20074258 ]
  3. De Ferrari GM, Dusi V: Drug safety evaluation of dronedarone in atrial fibrillation. Expert Opin Drug Saf. 2012 Nov;11(6):1023-45. doi: 10.1517/14740338.2012.722994. Epub 2012 Sep 13. [PubMed:22971242 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. FDA label

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. De Ferrari GM, Dusi V: Drug safety evaluation of dronedarone in atrial fibrillation. Expert Opin Drug Saf. 2012 Nov;11(6):1023-45. doi: 10.1517/14740338.2012.722994. Epub 2012 Sep 13. [PubMed:22971242 ]
  2. Schafer JA, Kjesbo NK, Gleason PP: Dronedarone: current evidence and future questions. Cardiovasc Ther. 2010 Spring;28(1):38-47. doi: 10.1111/j.1755-5922.2009.00112.x. [PubMed:20074258 ]
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Drug created on October 18, 2007 17:47 / Updated on May 29, 2016 02:12