You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameMacitentan
Accession NumberDB08932
TypeSmall Molecule
GroupsApproved
DescriptionMacitentan was approved in October 2013. It is indicated for patients with pulmonary arterial hypertension, and is marketed under the brand name Opsumit. Macitentan is an antagonist/blocker of endothelin receptors on blood vessels and smooth muscle, and, thus, blocks the stimulation of vasculature hypertrophy, inflammation, fibrosis, proliferation, and vasoconstriction. Similar to all drugs acting on the renin-angiotensin system, macitentan is associated with embryo and fetal toxicity, so it should not be used in pregnancy and has special precautions that must be followed for all females of child-bearing age.
Structure
Thumb
Synonyms
Macitentanum
External Identifiers
  • ACT 064992
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Opsumittablet, film coated10 mg/1oralActelion Pharmaceuticals US, Inc.2013-10-01Not applicableUs
Opsumittablet10 mgoralActelion Pharmaceuticals Ltd2014-01-15Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIZ9K9Y9WMVL
CAS number441798-33-0
WeightAverage: 588.273
Monoisotopic: 585.963349142
Chemical FormulaC19H20Br2N6O4S
InChI KeyJGCMEBMXRHSZKX-UHFFFAOYSA-N
InChI
InChI=1S/C19H20Br2N6O4S/c1-2-7-26-32(28,29)27-17-16(13-3-5-14(20)6-4-13)18(25-12-24-17)30-8-9-31-19-22-10-15(21)11-23-19/h3-6,10-12,26H,2,7-9H2,1H3,(H,24,25,27)
IUPAC Name
{[5-(4-bromophenyl)-6-{2-[(5-bromopyrimidin-2-yl)oxy]ethoxy}pyrimidin-4-yl]sulfamoyl}(propyl)amine
SMILES
CCCNS(=O)(=O)NC1=C(C(OCCOC2=NC=C(Br)C=N2)=NC=N1)C1=CC=C(Br)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpyrimidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrimidine ring through a CC or CN bond. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentPhenylpyrimidines
Alternative Parents
Substituents
  • 5-phenylpyrimidine
  • Halopyrimidine
  • Halobenzene
  • Bromobenzene
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Sulfuric acid diamide
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl bromide
  • Heteroaromatic compound
  • Organic sulfuric acid or derivatives
  • Azacycle
  • Ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organobromide
  • Organohalogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationMacitentan is indicated for patients with pulmonary arterial hypertension.
PharmacodynamicsMacitentan blocks simulators of hypertrophy, inflammation, fibrosis, proliferation, and vasoconstriction.
Mechanism of actionMacitentan is an antagonist/blocker of endothelin receptors. Endothelin receptors are found in the endothelial cells of blood vessels and smooth muscle. Macitentan binds to the receptors, endothelin A and B (ETA and ETB), which prevents the agonist endothelin -1 (ET-1) from binding and stimulating the ETA and ETB receptors.
Related Articles
AbsorptionMacitentan is administered orally, and it take about 8 hours for maximum plasma concentrations to be reached.
Volume of distribution

Macitentan has a volume of distribution of 50L.

Protein bindingMacitentan is >99% bound to plasma proteins, which are mainly albumin
Metabolism

Macitentan is metabolised to an active metabolite by CYP 3A4 (major) and CYP 2C19 (minor).

Route of eliminationEliminated 50% through urine and 24% through feces.
Half lifeThe half life of macitentan is 16 hours, and the half life of it's active metabolite is 48 hours.
Clearance

Clearance data was not found.

ToxicityMacitentan has a black box warning of embryo-fetal toxicity. Special precautions must be taken for all females of child-bearing age, and women who are pregnant must not be given macitentan.
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 AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral10 mg
Tablet, film coatedoral10 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7094781 No2002-10-122022-10-12Us
US8268847 No2009-04-182029-04-18Us
US8367685 No2008-10-042028-10-04Us
US9265762 No2007-05-292027-05-29Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityNot water solubleNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00668 mg/mLALOGPS
logP3.05ALOGPS
logP3.69ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)7.76ChemAxon
pKa (Strongest Basic)2.26ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area128.22 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity126.98 m3·mol-1ChemAxon
Polarizability50.55 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglarz M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T: The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N’-p ropylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem. 2012 Sep 13;55(17):7849-61. doi: 10.1021/jm3009103. Epub 2012 Aug 16. Pubmed

General References
  1. Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglarz M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T: The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-p ropylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem. 2012 Sep 13;55(17):7849-61. doi: 10.1021/jm3009103. Epub 2012 Aug 16. [PubMed:22862294 ]
External Links
ATC CodesC02KX04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (836 KB)
MSDSDownload (105 KB)
Interactions
Drug Interactions
Drug
7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE may increase the hypotensive activities of Macitentan.
AbirateroneThe metabolism of Macitentan can be decreased when combined with Abiraterone.
AcebutololAcebutolol may increase the hypotensive activities of Macitentan.
AlfuzosinAlfuzosin may increase the hypotensive activities of Macitentan.
AliskirenAliskiren may increase the hypotensive activities of Macitentan.
AlprenololAlprenolol may increase the hypotensive activities of Macitentan.
AmbrisentanAmbrisentan may increase the hypotensive activities of Macitentan.
AmifostineMacitentan may increase the hypotensive activities of Amifostine.
AmiodaroneThe serum concentration of Macitentan can be increased when it is combined with Amiodarone.
AmlodipineAmlodipine may increase the hypotensive activities of Macitentan.
AprepitantThe serum concentration of Macitentan can be increased when it is combined with Aprepitant.
ArmodafinilThe metabolism of Macitentan can be decreased when combined with Armodafinil.
AtazanavirThe serum concentration of Macitentan can be increased when it is combined with Atazanavir.
AtenololAtenolol may increase the hypotensive activities of Macitentan.
AtomoxetineThe metabolism of Macitentan can be decreased when combined with Atomoxetine.
BenazeprilBenazepril may increase the hypotensive activities of Macitentan.
BendroflumethiazideBendroflumethiazide may increase the hypotensive activities of Macitentan.
BenmoxinBenmoxin may increase the hypotensive activities of Macitentan.
BepridilBepridil may increase the hypotensive activities of Macitentan.
BetaxololBetaxolol may increase the hypotensive activities of Macitentan.
BethanidineBethanidine may increase the hypotensive activities of Macitentan.
BexaroteneThe serum concentration of Macitentan can be decreased when it is combined with Bexarotene.
BimatoprostBimatoprost may increase the hypotensive activities of Macitentan.
BisoprololBisoprolol may increase the hypotensive activities of Macitentan.
BoceprevirThe serum concentration of Macitentan can be increased when it is combined with Boceprevir.
BortezomibThe metabolism of Macitentan can be decreased when combined with Bortezomib.
BosentanThe serum concentration of Macitentan can be decreased when it is combined with Bosentan.
BosentanMacitentan may increase the hypotensive activities of Bosentan.
BretyliumBretylium may increase the hypotensive activities of Macitentan.
BrimonidineMacitentan may increase the hypotensive activities of Brimonidine.
BrimonidineBrimonidine may increase the antihypertensive activities of Macitentan.
BupranololBupranolol may increase the hypotensive activities of Macitentan.
CandesartanCandesartan may increase the hypotensive activities of Macitentan.
CandoxatrilCandoxatril may increase the hypotensive activities of Macitentan.
CaptoprilCaptopril may increase the hypotensive activities of Macitentan.
CarbamazepineThe serum concentration of Macitentan can be decreased when it is combined with Carbamazepine.
CaroxazoneCaroxazone may increase the hypotensive activities of Macitentan.
CarteololCarteolol may increase the hypotensive activities of Macitentan.
CarvedilolCarvedilol may increase the hypotensive activities of Macitentan.
CeliprololCeliprolol may increase the hypotensive activities of Macitentan.
CeritinibThe serum concentration of Macitentan can be increased when it is combined with Ceritinib.
ChloramphenicolThe metabolism of Macitentan can be decreased when combined with Chloramphenicol.
ChlorothiazideChlorothiazide may increase the hypotensive activities of Macitentan.
ChlorthalidoneChlorthalidone may increase the hypotensive activities of Macitentan.
CholecalciferolThe metabolism of Macitentan can be decreased when combined with Cholecalciferol.
CilazaprilCilazapril may increase the hypotensive activities of Macitentan.
CimetidineThe metabolism of Macitentan can be decreased when combined with Cimetidine.
CitalopramThe metabolism of Macitentan can be decreased when combined with Citalopram.
ClarithromycinThe serum concentration of Macitentan can be increased when it is combined with Clarithromycin.
ClemastineThe metabolism of Macitentan can be decreased when combined with Clemastine.
ClonidineClonidine may increase the hypotensive activities of Macitentan.
ClotrimazoleThe metabolism of Macitentan can be decreased when combined with Clotrimazole.
CobicistatThe serum concentration of Macitentan can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Macitentan can be increased when it is combined with Conivaptan.
CrizotinibThe metabolism of Macitentan can be decreased when combined with Crizotinib.
CryptenamineCryptenamine may increase the hypotensive activities of Macitentan.
CyclosporineThe metabolism of Macitentan can be decreased when combined with Cyclosporine.
CyclothiazideCyclothiazide may increase the hypotensive activities of Macitentan.
DabrafenibThe serum concentration of Macitentan can be decreased when it is combined with Dabrafenib.
DarunavirThe serum concentration of Macitentan can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Macitentan can be increased when it is combined with Dasatinib.
DebrisoquinDebrisoquin may increase the hypotensive activities of Macitentan.
DeferasiroxThe serum concentration of Macitentan can be decreased when it is combined with Deferasirox.
DelavirdineThe metabolism of Macitentan can be decreased when combined with Delavirdine.
DeserpidineDeserpidine may increase the hypotensive activities of Macitentan.
DexamethasoneThe serum concentration of Macitentan can be decreased when it is combined with Dexamethasone.
DiazoxideDiazoxide may increase the hypotensive activities of Macitentan.
DihydroergotamineThe metabolism of Macitentan can be decreased when combined with Dihydroergotamine.
DiltiazemDiltiazem may increase the hypotensive activities of Macitentan.
DorzolamideDorzolamide may increase the hypotensive activities of Macitentan.
DoxazosinDoxazosin may increase the hypotensive activities of Macitentan.
DoxycyclineThe metabolism of Macitentan can be decreased when combined with Doxycycline.
DronedaroneThe metabolism of Macitentan can be decreased when combined with Dronedarone.
EfavirenzThe serum concentration of Macitentan can be decreased when it is combined with Efavirenz.
EfonidipineEfonidipine may increase the hypotensive activities of Macitentan.
EnalaprilEnalapril may increase the hypotensive activities of Macitentan.
EnalaprilatEnalaprilat may increase the hypotensive activities of Macitentan.
EnzalutamideThe serum concentration of Macitentan can be decreased when it is combined with Enzalutamide.
EpoprostenolEpoprostenol may increase the hypotensive activities of Macitentan.
EprosartanEprosartan may increase the hypotensive activities of Macitentan.
ErythromycinThe metabolism of Macitentan can be decreased when combined with Erythromycin.
Eslicarbazepine acetateThe serum concentration of Macitentan can be decreased when it is combined with Eslicarbazepine acetate.
EsomeprazoleThe metabolism of Macitentan can be decreased when combined with Esomeprazole.
EtravirineThe serum concentration of Macitentan can be decreased when it is combined with Etravirine.
FelodipineFelodipine may increase the hypotensive activities of Macitentan.
FenoldopamFenoldopam may increase the hypotensive activities of Macitentan.
FluconazoleThe metabolism of Macitentan can be decreased when combined with Fluconazole.
FluoxetineThe metabolism of Macitentan can be decreased when combined with Fluoxetine.
FluvoxamineThe metabolism of Macitentan can be decreased when combined with Fluvoxamine.
FosamprenavirThe metabolism of Macitentan can be decreased when combined with Fosamprenavir.
FosaprepitantThe serum concentration of Macitentan can be increased when it is combined with Fosaprepitant.
FosinoprilFosinopril may increase the hypotensive activities of Macitentan.
FosphenytoinThe serum concentration of Macitentan can be decreased when it is combined with Fosphenytoin.
FurazolidoneFurazolidone may increase the hypotensive activities of Macitentan.
Fusidic AcidThe serum concentration of Macitentan can be increased when it is combined with Fusidic Acid.
GemfibrozilThe metabolism of Macitentan can be decreased when combined with Gemfibrozil.
GuanabenzGuanabenz may increase the hypotensive activities of Macitentan.
GuanadrelGuanadrel may increase the hypotensive activities of Macitentan.
GuanethidineGuanethidine may increase the hypotensive activities of Macitentan.
GuanfacineGuanfacine may increase the hypotensive activities of Macitentan.
HexamethoniumHexamethonium may increase the hypotensive activities of Macitentan.
HydracarbazineHydracarbazine may increase the hypotensive activities of Macitentan.
HydralazineHydralazine may increase the hypotensive activities of Macitentan.
HydrochlorothiazideHydrochlorothiazide may increase the hypotensive activities of Macitentan.
HydroflumethiazideHydroflumethiazide may increase the hypotensive activities of Macitentan.
IdelalisibThe serum concentration of Macitentan can be increased when it is combined with Idelalisib.
IloprostIloprost may increase the hypotensive activities of Macitentan.
ImatinibThe metabolism of Macitentan can be decreased when combined with Imatinib.
IndapamideIndapamide may increase the hypotensive activities of Macitentan.
IndenololIndenolol may increase the hypotensive activities of Macitentan.
IndinavirThe serum concentration of Macitentan can be increased when it is combined with Indinavir.
IndoraminIndoramin may increase the hypotensive activities of Macitentan.
IproclozideIproclozide may increase the hypotensive activities of Macitentan.
IproniazidIproniazid may increase the hypotensive activities of Macitentan.
IrbesartanIrbesartan may increase the hypotensive activities of Macitentan.
IsavuconazoniumThe metabolism of Macitentan can be decreased when combined with Isavuconazonium.
IsocarboxazidIsocarboxazid may increase the hypotensive activities of Macitentan.
IsoniazidThe metabolism of Macitentan can be decreased when combined with Isoniazid.
IsradipineIsradipine may increase the hypotensive activities of Macitentan.
ItraconazoleThe serum concentration of Macitentan can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Macitentan can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Macitentan can be increased when it is combined with Ketoconazole.
LabetalolLabetalol may increase the hypotensive activities of Macitentan.
LacidipineLacidipine may increase the hypotensive activities of Macitentan.
LatanoprostLatanoprost may increase the hypotensive activities of Macitentan.
LercanidipineLercanidipine may increase the hypotensive activities of Macitentan.
LisinoprilLisinopril may increase the hypotensive activities of Macitentan.
LofexidineLofexidine may increase the hypotensive activities of Macitentan.
LopinavirThe serum concentration of Macitentan can be increased when it is combined with Lopinavir.
LosartanLosartan may increase the hypotensive activities of Macitentan.
LovastatinThe metabolism of Macitentan can be decreased when combined with Lovastatin.
LuliconazoleThe serum concentration of Macitentan can be increased when it is combined with Luliconazole.
LumacaftorThe serum concentration of Macitentan can be decreased when it is combined with Lumacaftor.
ManidipineManidipine may increase the hypotensive activities of Macitentan.
MebanazineMebanazine may increase the hypotensive activities of Macitentan.
MecamylamineMecamylamine may increase the hypotensive activities of Macitentan.
MethyldopaMethyldopa may increase the hypotensive activities of Macitentan.
Methylene blueMethylene blue may increase the hypotensive activities of Macitentan.
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Macitentan.
MetipranololMetipranolol may increase the hypotensive activities of Macitentan.
MetolazoneMetolazone may increase the hypotensive activities of Macitentan.
MetoprololMetoprolol may increase the hypotensive activities of Macitentan.
MibefradilMibefradil may increase the hypotensive activities of Macitentan.
MifepristoneThe metabolism of Macitentan can be decreased when combined with Mifepristone.
MinaprineMinaprine may increase the hypotensive activities of Macitentan.
MinoxidilMinoxidil may increase the hypotensive activities of Macitentan.
MitotaneThe serum concentration of Macitentan can be decreased when it is combined with Mitotane.
MoclobemideMoclobemide may increase the hypotensive activities of Macitentan.
ModafinilThe serum concentration of Macitentan can be decreased when it is combined with Modafinil.
MoexiprilMoexipril may increase the hypotensive activities of Macitentan.
MolsidomineMolsidomine may increase the hypotensive activities of Macitentan.
MoxonidineMoxonidine may increase the hypotensive activities of Macitentan.
NadololNadolol may increase the hypotensive activities of Macitentan.
NafcillinThe serum concentration of Macitentan can be decreased when it is combined with Nafcillin.
NebivololNebivolol may increase the hypotensive activities of Macitentan.
NefazodoneThe serum concentration of Macitentan can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Macitentan can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Macitentan can be increased when it is combined with Netupitant.
NevirapineThe serum concentration of Macitentan can be decreased when it is combined with Nevirapine.
NialamideNialamide may increase the hypotensive activities of Macitentan.
NicardipineNicardipine may increase the hypotensive activities of Macitentan.
NicorandilNicorandil may increase the hypotensive activities of Macitentan.
NiguldipineNiguldipine may increase the hypotensive activities of Macitentan.
NilotinibThe metabolism of Macitentan can be decreased when combined with Nilotinib.
NilvadipineNilvadipine may increase the hypotensive activities of Macitentan.
NimodipineNimodipine may increase the hypotensive activities of Macitentan.
NisoldipineNisoldipine may increase the hypotensive activities of Macitentan.
NitrendipineNitrendipine may increase the hypotensive activities of Macitentan.
NitroprussideNitroprusside may increase the hypotensive activities of Macitentan.
ObinutuzumabMacitentan may increase the hypotensive activities of Obinutuzumab.
OctamoxinOctamoxin may increase the hypotensive activities of Macitentan.
OlaparibThe metabolism of Macitentan can be decreased when combined with Olaparib.
OlmesartanOlmesartan may increase the hypotensive activities of Macitentan.
OmapatrilatOmapatrilat may increase the hypotensive activities of Macitentan.
OmeprazoleThe metabolism of Macitentan can be decreased when combined with Omeprazole.
OsimertinibThe serum concentration of Macitentan can be increased when it is combined with Osimertinib.
OxprenololOxprenolol may increase the hypotensive activities of Macitentan.
PalbociclibThe serum concentration of Macitentan can be increased when it is combined with Palbociclib.
PantoprazoleThe metabolism of Macitentan can be decreased when combined with Pantoprazole.
PargylinePargyline may increase the hypotensive activities of Macitentan.
PenbutololPenbutolol may increase the hypotensive activities of Macitentan.
PentobarbitalThe serum concentration of Macitentan can be decreased when it is combined with Pentobarbital.
PentoliniumPentolinium may increase the hypotensive activities of Macitentan.
PentoxifyllinePentoxifylline may increase the hypotensive activities of Macitentan.
PerindoprilPerindopril may increase the hypotensive activities of Macitentan.
PhenelzinePhenelzine may increase the hypotensive activities of Macitentan.
PheniprazinePheniprazine may increase the hypotensive activities of Macitentan.
PhenobarbitalThe serum concentration of Macitentan can be decreased when it is combined with Phenobarbital.
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Macitentan.
PhenoxypropazinePhenoxypropazine may increase the hypotensive activities of Macitentan.
PhentolaminePhentolamine may increase the hypotensive activities of Macitentan.
PhenytoinThe serum concentration of Macitentan can be decreased when it is combined with Phenytoin.
PinacidilPinacidil may increase the hypotensive activities of Macitentan.
PindololPindolol may increase the hypotensive activities of Macitentan.
PirlindolePirlindole may increase the hypotensive activities of Macitentan.
PivhydrazinePivhydrazine may increase the hypotensive activities of Macitentan.
PolythiazidePolythiazide may increase the hypotensive activities of Macitentan.
PosaconazoleThe serum concentration of Macitentan can be increased when it is combined with Posaconazole.
PrazosinPrazosin may increase the hypotensive activities of Macitentan.
PrimidoneThe serum concentration of Macitentan can be decreased when it is combined with Primidone.
PropranololPropranolol may increase the hypotensive activities of Macitentan.
QuinaprilQuinapril may increase the hypotensive activities of Macitentan.
QuinineQuinine may increase the hypotensive activities of Macitentan.
RamiprilRamipril may increase the hypotensive activities of Macitentan.
RanolazineThe metabolism of Macitentan can be decreased when combined with Ranolazine.
RasagilineRasagiline may increase the hypotensive activities of Macitentan.
RemikirenRemikiren may increase the hypotensive activities of Macitentan.
RescinnamineRescinnamine may increase the hypotensive activities of Macitentan.
ReserpineReserpine may increase the hypotensive activities of Macitentan.
RifabutinThe serum concentration of Macitentan can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Macitentan can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Macitentan can be decreased when it is combined with Rifapentine.
RiociguatRiociguat may increase the hypotensive activities of Macitentan.
RitonavirThe serum concentration of Macitentan can be increased when it is combined with Ritonavir.
RituximabMacitentan may increase the hypotensive activities of Rituximab.
SafrazineSafrazine may increase the hypotensive activities of Macitentan.
SaprisartanSaprisartan may increase the hypotensive activities of Macitentan.
SaquinavirThe serum concentration of Macitentan can be increased when it is combined with Saquinavir.
SelegilineSelegiline may increase the hypotensive activities of Macitentan.
SelexipagSelexipag may increase the hypotensive activities of Macitentan.
SertralineThe metabolism of Macitentan can be decreased when combined with Sertraline.
SildenafilSildenafil may increase the antihypertensive activities of Macitentan.
SiltuximabThe serum concentration of Macitentan can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Macitentan can be increased when it is combined with Simeprevir.
SitaxentanSitaxentan may increase the hypotensive activities of Macitentan.
SpiraprilSpirapril may increase the hypotensive activities of Macitentan.
St. John's WortThe serum concentration of Macitentan can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Macitentan can be increased when it is combined with Stiripentol.
SulfisoxazoleThe metabolism of Macitentan can be decreased when combined with Sulfisoxazole.
TadalafilTadalafil may increase the antihypertensive activities of Macitentan.
TelaprevirThe serum concentration of Macitentan can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Macitentan can be increased when it is combined with Telithromycin.
TelmisartanTelmisartan may increase the hypotensive activities of Macitentan.
TemocaprilTemocapril may increase the hypotensive activities of Macitentan.
TerlipressinTerlipressin may increase the hypotensive activities of Macitentan.
TiboloneTibolone may increase the hypotensive activities of Macitentan.
TiclopidineThe metabolism of Macitentan can be decreased when combined with Ticlopidine.
TicrynafenTicrynafen may increase the hypotensive activities of Macitentan.
TimololTimolol may increase the hypotensive activities of Macitentan.
TocilizumabThe serum concentration of Macitentan can be decreased when it is combined with Tocilizumab.
TolazolineTolazoline may increase the hypotensive activities of Macitentan.
ToloxatoneToloxatone may increase the hypotensive activities of Macitentan.
TopiramateThe metabolism of Macitentan can be decreased when combined with Topiramate.
TorasemideTorasemide may increase the hypotensive activities of Macitentan.
TrandolaprilTrandolapril may increase the hypotensive activities of Macitentan.
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypotensive activities of Macitentan.
TranylcypromineTranylcypromine may increase the hypotensive activities of Macitentan.
TravoprostTravoprost may increase the hypotensive activities of Macitentan.
TreprostinilTreprostinil may increase the hypotensive activities of Macitentan.
TrichlormethiazideTrichlormethiazide may increase the hypotensive activities of Macitentan.
TrimazosinTrimazosin may increase the hypotensive activities of Macitentan.
TrimethaphanTrimethaphan may increase the hypotensive activities of Macitentan.
UdenafilUdenafil may increase the antihypertensive activities of Macitentan.
UnoprostoneUnoprostone may increase the hypotensive activities of Macitentan.
ValsartanValsartan may increase the hypotensive activities of Macitentan.
VardenafilVardenafil may increase the antihypertensive activities of Macitentan.
VenlafaxineThe metabolism of Macitentan can be decreased when combined with Venlafaxine.
VerapamilThe metabolism of Macitentan can be decreased when combined with Verapamil.
VoriconazoleThe serum concentration of Macitentan can be increased when it is combined with Voriconazole.
XylometazolineXylometazoline may increase the hypotensive activities of Macitentan.
YohimbineYohimbine may decrease the antihypertensive activities of Macitentan.
ZiprasidoneThe metabolism of Macitentan can be decreased when combined with Ziprasidone.
Food Interactions
  • Can be taken with or without food.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3.
Gene Name:
EDNRA
Uniprot ID:
P25101
Molecular Weight:
48721.76 Da
References
  1. Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglarz M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T: The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-p ropylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem. 2012 Sep 13;55(17):7849-61. doi: 10.1021/jm3009103. Epub 2012 Aug 16. [PubMed:22862294 ]
  2. Bruderer S, Hopfgartner G, Seiberling M, Wank J, Sidharta PN, Treiber A, Dingemanse J: Absorption, distribution, metabolism, and excretion of macitentan, a dual endothelin receptor antagonist, in humans. Xenobiotica. 2012 Sep;42(9):901-10. doi: 10.3109/00498254.2012.664665. Epub 2012 Mar 30. [PubMed:22458347 ]
  3. Dingemanse J, Sidharta PN, Maddrey WC, Rubin LJ, Mickail H: Efficacy, safety and clinical pharmacology of macitentan in comparison to other endothelin receptor antagonists in the treatment of pulmonary arterial hypertension. Expert Opin Drug Saf. 2014 Mar;13(3):391-405. doi: 10.1517/14740338.2014.859674. Epub 2013 Nov 22. [PubMed:24261583 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Peptide hormone binding
Specific Function:
Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Gene Name:
EDNRB
Uniprot ID:
P24530
Molecular Weight:
49643.255 Da
References
  1. Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglarz M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T: The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-p ropylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem. 2012 Sep 13;55(17):7849-61. doi: 10.1021/jm3009103. Epub 2012 Aug 16. [PubMed:22862294 ]
  2. Bruderer S, Hopfgartner G, Seiberling M, Wank J, Sidharta PN, Treiber A, Dingemanse J: Absorption, distribution, metabolism, and excretion of macitentan, a dual endothelin receptor antagonist, in humans. Xenobiotica. 2012 Sep;42(9):901-10. doi: 10.3109/00498254.2012.664665. Epub 2012 Mar 30. [PubMed:22458347 ]
  3. Dingemanse J, Sidharta PN, Maddrey WC, Rubin LJ, Mickail H: Efficacy, safety and clinical pharmacology of macitentan in comparison to other endothelin receptor antagonists in the treatment of pulmonary arterial hypertension. Expert Opin Drug Saf. 2014 Mar;13(3):391-405. doi: 10.1517/14740338.2014.859674. Epub 2013 Nov 22. [PubMed:24261583 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
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
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da

Carriers

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
binder
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
Comments
comments powered by Disqus
Drug created on December 29, 2013 11:30 / Updated on October 01, 2016 02:31