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Identification
NameBosentan
Accession NumberDB00559  (APRD00829)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Bosentan is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer®. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure.

Structure
Thumb
Synonyms
4-(1,1-Dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-(2,2'-bipyrimidin)-4-yl) benzenesulfornamide
bosentán
bosentan
bosentanum
p-tert-Butyl-N-(6-(2-hydroxyethoxy)-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl)benzenesulfonamide
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel-bosentantablet125 mgoralAccel Pharma IncNot applicableNot applicableCanada
Act Bosentantablet125 mgoralActavis Pharma Company2012-06-05Not applicableCanada
Act Bosentantablet62.5 mgoralActavis Pharma Company2012-06-05Not applicableCanada
Bosentan Tabletstablet125 mgoralAccord Healthcare Inc2014-11-132015-06-02Canada
Ipg-bosentantablet62.5 mgoralInternational Pharmaceutical Generics LtdNot applicableNot applicableCanada
Ipg-bosentantablet125 mgoralInternational Pharmaceutical Generics LtdNot applicableNot applicableCanada
Mar-bosentantablet125 mgoralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Mar-bosentantablet62.5 mgoralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Mylan-bosentantablet62.5 mgoralMylan Pharmaceuticals Ulc2012-05-29Not applicableCanada
Mylan-bosentantablet125.0 mgoralMylan Pharmaceuticals Ulc2012-05-29Not applicableCanada
PMS-bosentantablet125 mgoralPharmascience Inc2012-06-12Not applicableCanada
PMS-bosentantablet62.5 mgoralPharmascience Inc2012-06-12Not applicableCanada
Sandoz Bosentantablet125 mgoralSandoz Canada Incorporated2012-06-13Not applicableCanada
Sandoz Bosentantablet62.5 mgoralSandoz Canada Incorporated2012-06-13Not applicableCanada
Teva-bosentantablet125.0 mgoralTeva Canada Limited2012-12-28Not applicableCanada
Teva-bosentantablet62.5 mgoralTeva Canada Limited2012-12-12Not applicableCanada
Tracleertablet, film coated62.5 mg/1oralActelion Pharmaceuticals US, Inc.2001-11-20Not applicableUs
Tracleertablet125 mgoralActelion Pharmaceuticals Ltd2001-12-14Not applicableCanada
Tracleertablet62.5 mgoralActelion Pharmaceuticals Ltd2001-12-14Not applicableCanada
Tracleertablet, film coated125 mg/1oralActelion Pharmaceuticals US, Inc.2001-11-20Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-bosentantablet62.5 mgoralApotex IncNot applicableNot applicableCanada
Apo-bosentantablet125.0 mgoralApotex IncNot applicableNot applicableCanada
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Bosentan monohydrate
157212-55-0
Thumb
  • InChI Key: SXTRWVVIEPWAKM-UHFFFAOYSA-N
  • Monoisotopic Mass: 569.194419532
  • Average Mass: 569.63
DBSALT001842
Categories
UNIIXUL93R30K2
CAS number147536-97-8
WeightAverage: 551.614
Monoisotopic: 551.183854375
Chemical FormulaC27H29N5O6S
InChI KeyInChIKey=GJPICJJJRGTNOD-UHFFFAOYSA-N
InChI
InChI=1S/C27H29N5O6S/c1-27(2,3)18-10-12-19(13-11-18)39(34,35)32-23-22(38-21-9-6-5-8-20(21)36-4)26(37-17-16-33)31-25(30-23)24-28-14-7-15-29-24/h5-15,33H,16-17H2,1-4H3,(H,30,31,32)
IUPAC Name
4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide
SMILES
COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)N=C(N=C1OCCO)C1=NC=CC=N1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as bipyrimidines and oligopyrimidines. These are organic compounds containing two or more pyrimidine rings directly linked to each other. 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 ParentBipyrimidines and oligopyrimidines
Alternative Parents
Substituents
  • Bipyrimidine
  • Diaryl ether
  • Benzenesulfonamide
  • Phenylpropane
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Azacycle
  • Ether
  • Hydrocarbon derivative
  • Primary alcohol
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed in the treatment of pulmonary arterial hypertension (PAH), to improve exercise ability and to decrease the rate of clinical worsening (in patients with WHO Class III or IV symptoms).
PharmacodynamicsBosentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Bosentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects.
Mechanism of actionEndothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ETA and ETB receptors in the endothelium and vascular smooth muscle. ET-1 concentrations are elevated in plasma and lung tissue of patients with pulmonary arterial hypertension, suggesting a pathogenic role for ET-1 in this disease. Bosentan is a specific and competitive antagonist at endothelin receptor types ETA and ETB. Bosentan has a slightly higher affinity for ETA receptors than for ETB receptors.
Related Articles
AbsorptionAbsolute bioavailability is approximately 50% and food does not affect absorption.
Volume of distribution
  • 18 L
Protein bindingGreater than 98% to plasma proteins, mainly albumin.
Metabolism

Bosentan is metabolized in the liver by the cytochrome P450 enzymes CYP2C9 and CYP3A4 (and possibly CYP2C19), producing three metabolites, one of which, Ro 48-5033, is pharmacologically active and may contribute 10 to 20% to the total activity of the parent compound.

SubstrateEnzymesProduct
Bosentan
Bosentan metabolite Ro 48-5033Details
Bosentan
Bosentan metabolite Ro 47-8634Details
Bosentan metabolite Ro 48-5033
Not Available
Bosentan metabolite Ro 64-1056Details
Bosentan metabolite Ro 47-8634
Not Available
Bosentan metabolite Ro 64-1056Details
Route of eliminationBosentan is eliminated by biliary excretion following metabolism in the liver.
Half lifeTerminal elimination half-life is about 5 hours in healthy adult subjects.
Clearance
  • 4 L/h [patients with pulmonary arterial hypertension]
ToxicityBosentan has been given as a single dose of up to 2400 mg in normal volunteers, or up to 2000 mg/day for 2 months in patients, without any major clinical consequences. The most common side effect was headache of mild to moderate intensity. In the cyclosporine A interaction study, in which doses of 500 and 1000 mg b.i.d. of bosentan were given concomitantly with cyclosporine A, trough plasma concentrations of bosentan increased 30-fold, resulting in severe headache, nausea, and vomiting, but no serious adverse events. Mild decreases in blood pressure and increases in heart rate were observed. There is no specific experience of overdosage with bosentan beyond the doses described above. Massive overdosage may result in pronounced hypotension requiring active cardiovascular support.
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+0.9253
Blood Brain Barrier-0.7419
Caco-2 permeable-0.8956
P-glycoprotein substrateNon-substrate0.5738
P-glycoprotein inhibitor INon-inhibitor0.6175
P-glycoprotein inhibitor IINon-inhibitor0.5092
Renal organic cation transporterNon-inhibitor0.9149
CYP450 2C9 substrateNon-substrate0.5926
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.5132
CYP450 1A2 substrateNon-inhibitor0.7203
CYP450 2C9 inhibitorInhibitor0.518
CYP450 2D6 inhibitorNon-inhibitor0.8755
CYP450 2C19 inhibitorNon-inhibitor0.5219
CYP450 3A4 inhibitorInhibitor0.8407
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.772
Ames testNon AMES toxic0.6147
CarcinogenicityNon-carcinogens0.6515
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2676 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9679
hERG inhibition (predictor II)Non-inhibitor0.572
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Actelion ltd
Packagers
Dosage forms
FormRouteStrength
Tabletoral125.0 mg
Tabletoral125 mg
Tabletoral62.5 mg
Tablet, film coatedoral125 mg/1
Tablet, film coatedoral62.5 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2071193 No1998-08-252012-06-12Canada
US5292740 No1995-11-202015-11-20Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityPoorly soluble in water (1.0 mg/100 ml) and in aqueous solutions at low pH (0.1 mg/100 ml at pH 1.1 and 4.0; 0.2 mg/100 ml at pH 5.0). Solubility increases at higher pH values (43 mg/100 ml at pH 7.5).Not Available
logP3.7Not Available
Caco2 permeability-5.98ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.00904 mg/mLALOGPS
logP4.18ALOGPS
logP4.94ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)5.8ChemAxon
pKa (Strongest Basic)-0.43ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area145.65 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity166.66 m3·mol-1ChemAxon
Polarizability57.89 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
References
Synthesis Reference

Maurizio TADDEI, Diletta Naldini, Pietro Allegrini, Gabriele Razzetti, Simone Mantegazza, “Process for the Preparation of Bosentan.” U.S. Patent US20090156811, issued June 18, 2009.

US20090156811
General ReferencesNot Available
External Links
ATC CodesC02KX01
AHFS Codes
  • 24:12.92
PDB EntriesNot Available
FDA labelDownload (424 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Abiraterone can be decreased when it is combined with Bosentan.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Bosentan.
AlfuzosinThe serum concentration of Alfuzosin can be decreased when it is combined with Bosentan.
AlprazolamThe serum concentration of Alprazolam can be decreased when it is combined with Bosentan.
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Bosentan.
AmiodaroneThe serum concentration of Amiodarone can be decreased when it is combined with Bosentan.
AmlodipineThe serum concentration of Amlodipine can be decreased when it is combined with Bosentan.
ApixabanThe serum concentration of Apixaban can be decreased when it is combined with Bosentan.
ApremilastThe serum concentration of Apremilast can be decreased when it is combined with Bosentan.
AprepitantThe serum concentration of Aprepitant can be decreased when it is combined with Bosentan.
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Bosentan.
ArmodafinilThe serum concentration of Armodafinil can be decreased when it is combined with Bosentan.
AtazanavirThe serum concentration of Atazanavir can be decreased when it is combined with Bosentan.
AtorvastatinThe metabolism of Atorvastatin can be increased when combined with Bosentan.
AvanafilThe serum concentration of Avanafil can be decreased when it is combined with Bosentan.
AxitinibThe serum concentration of Axitinib can be decreased when it is combined with Bosentan.
BedaquilineThe serum concentration of Bedaquiline can be decreased when it is combined with Bosentan.
BenzphetamineThe serum concentration of Benzphetamine can be decreased when it is combined with Bosentan.
BisoprololThe serum concentration of Bisoprolol can be decreased when it is combined with Bosentan.
BoceprevirThe serum concentration of Boceprevir can be decreased when it is combined with Bosentan.
BortezomibThe serum concentration of Bortezomib can be decreased when it is combined with Bosentan.
BosutinibThe serum concentration of Bosutinib can be decreased when it is combined with Bosentan.
BrexpiprazoleThe serum concentration of Brexpiprazole can be decreased when it is combined with Bosentan.
BuprenorphineThe serum concentration of Buprenorphine can be decreased when it is combined with Bosentan.
BuspironeThe serum concentration of Buspirone can be decreased when it is combined with Bosentan.
CabazitaxelThe serum concentration of Cabazitaxel can be decreased when it is combined with Bosentan.
CabozantinibThe serum concentration of Cabozantinib can be decreased when it is combined with Bosentan.
CalcitriolThe serum concentration of Calcitriol can be decreased when it is combined with Bosentan.
CapecitabineThe serum concentration of Bosentan can be increased when it is combined with Capecitabine.
CarbamazepineThe serum concentration of Carbamazepine can be decreased when it is combined with Bosentan.
CeritinibThe serum concentration of Ceritinib can be decreased when it is combined with Bosentan.
ChlordiazepoxideThe serum concentration of Chlordiazepoxide can be decreased when it is combined with Bosentan.
ChloroquineThe serum concentration of Chloroquine can be decreased when it is combined with Bosentan.
ChlorotrianiseneThe serum concentration of Chlorotrianisene can be decreased when it is combined with Bosentan.
CilostazolThe serum concentration of Cilostazol can be decreased when it is combined with Bosentan.
CitalopramThe serum concentration of Citalopram can be decreased when it is combined with Bosentan.
ClarithromycinThe serum concentration of the active metabolites of Clarithromycin can be increased when Clarithromycin is used in combination with Bosentan.
ClonazepamThe serum concentration of Clonazepam can be decreased when it is combined with Bosentan.
ClorazepateThe serum concentration of Clorazepate can be decreased when it is combined with Bosentan.
CobicistatThe serum concentration of Bosentan can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Conivaptan can be decreased when it is combined with Bosentan.
CrizotinibThe serum concentration of Crizotinib can be decreased when it is combined with Bosentan.
CyclosporineThe serum concentration of Bosentan can be increased when it is combined with Cyclosporine.
Cyproterone acetateThe serum concentration of Cyproterone acetate can be decreased when it is combined with Bosentan.
DaclatasvirThe serum concentration of Daclatasvir can be decreased when it is combined with Bosentan.
DantroleneThe serum concentration of Dantrolene can be decreased when it is combined with Bosentan.
DapsoneThe serum concentration of Dapsone can be decreased when it is combined with Bosentan.
DarifenacinThe serum concentration of Darifenacin can be decreased when it is combined with Bosentan.
DarunavirThe serum concentration of Darunavir can be decreased when it is combined with Bosentan.
DasatinibThe serum concentration of Dasatinib can be decreased when it is combined with Bosentan.
DelavirdineThe serum concentration of Delavirdine can be decreased when it is combined with Bosentan.
DexamethasoneThe serum concentration of Dexamethasone can be decreased when it is combined with Bosentan.
DiazepamThe serum concentration of Diazepam can be decreased when it is combined with Bosentan.
DicoumarolThe metabolism of Dicoumarol can be increased when combined with Bosentan.
DienogestThe serum concentration of Dienogest can be decreased when it is combined with Bosentan.
DiltiazemThe serum concentration of Diltiazem can be decreased when it is combined with Bosentan.
DisopyramideThe serum concentration of Disopyramide can be decreased when it is combined with Bosentan.
DocetaxelThe serum concentration of Docetaxel can be decreased when it is combined with Bosentan.
DoxazosinThe serum concentration of Doxazosin can be decreased when it is combined with Bosentan.
DoxorubicinThe serum concentration of Doxorubicin can be decreased when it is combined with Bosentan.
DronedaroneThe serum concentration of Dronedarone can be decreased when it is combined with Bosentan.
EfavirenzThe serum concentration of Efavirenz can be decreased when it is combined with Bosentan.
EliglustatThe serum concentration of Eliglustat can be decreased when it is combined with Bosentan.
EltrombopagThe serum concentration of Bosentan can be increased when it is combined with Eltrombopag.
ElvitegravirThe serum concentration of Elvitegravir can be decreased when it is combined with Bosentan.
EnzalutamideThe serum concentration of Enzalutamide can be decreased when it is combined with Bosentan.
EplerenoneThe serum concentration of Eplerenone can be decreased when it is combined with Bosentan.
ErlotinibThe serum concentration of Erlotinib can be decreased when it is combined with Bosentan.
ErythromycinThe serum concentration of Erythromycin can be decreased when it is combined with Bosentan.
EscitalopramThe serum concentration of Escitalopram can be decreased when it is combined with Bosentan.
EstradiolThe serum concentration of Estradiol can be decreased when it is combined with Bosentan.
Estrone sulfateThe serum concentration of Estropipate can be decreased when it is combined with Bosentan.
EszopicloneThe serum concentration of Eszopiclone can be decreased when it is combined with Bosentan.
EthosuximideThe serum concentration of Ethosuximide can be decreased when it is combined with Bosentan.
EtonogestrelThe serum concentration of Etonogestrel can be decreased when it is combined with Bosentan.
EtoposideThe serum concentration of Etoposide can be decreased when it is combined with Bosentan.
EtravirineThe serum concentration of Etravirine can be decreased when it is combined with Bosentan.
EverolimusThe serum concentration of Everolimus can be decreased when it is combined with Bosentan.
ExemestaneThe serum concentration of Exemestane can be decreased when it is combined with Bosentan.
FelbamateThe serum concentration of Felbamate can be decreased when it is combined with Bosentan.
FelodipineThe serum concentration of Felodipine can be decreased when it is combined with Bosentan.
FentanylThe serum concentration of Fentanyl can be decreased when it is combined with Bosentan.
FesoterodineThe serum concentration of Fesoterodine can be decreased when it is combined with Bosentan.
FlibanserinThe serum concentration of Flibanserin can be decreased when it is combined with Bosentan.
FloxuridineThe serum concentration of Bosentan can be increased when it is combined with Floxuridine.
FluconazoleThe serum concentration of Bosentan can be increased when it is combined with Fluconazole.
FlunisolideThe serum concentration of Flunisolide can be decreased when it is combined with Bosentan.
FluorouracilThe serum concentration of Bosentan can be increased when it is combined with Fluorouracil.
FlurazepamThe serum concentration of Flurazepam can be decreased when it is combined with Bosentan.
FlutamideThe serum concentration of Flutamide can be decreased when it is combined with Bosentan.
FluvastatinThe serum concentration of Bosentan can be increased when it is combined with Fluvastatin.
FosamprenavirThe serum concentration of Fosamprenavir can be decreased when it is combined with Bosentan.
FosaprepitantThe serum concentration of Fosaprepitant can be decreased when it is combined with Bosentan.
GefitinibThe serum concentration of Gefitinib can be decreased when it is combined with Bosentan.
GemfibrozilThe serum concentration of Bosentan can be increased when it is combined with Gemfibrozil.
GlyburideGlyburide may increase the hepatotoxic activities of Bosentan.
GuanfacineThe serum concentration of Guanfacine can be decreased when it is combined with Bosentan.
HaloperidolThe serum concentration of Haloperidol can be decreased when it is combined with Bosentan.
HydrocodoneThe serum concentration of Hydrocodone can be decreased when it is combined with Bosentan.
Hydroxyprogesterone caproateThe serum concentration of Hydroxyprogesterone caproate can be decreased when it is combined with Bosentan.
IbrutinibThe serum concentration of Ibrutinib can be decreased when it is combined with Bosentan.
IdelalisibThe serum concentration of Idelalisib can be decreased when it is combined with Bosentan.
IfosfamideThe serum concentration of the active metabolites of Ifosfamide can be reduced when Ifosfamide is used in combination with Bosentan resulting in a loss in efficacy.
ImatinibThe serum concentration of Imatinib can be decreased when it is combined with Bosentan.
IndinavirThe serum concentration of Bosentan can be increased when it is combined with Indinavir.
IrbesartanThe serum concentration of Bosentan can be increased when it is combined with Irbesartan.
IrinotecanThe serum concentration of Irinotecan can be decreased when it is combined with Bosentan.
IsavuconazoniumThe serum concentration of Isavuconazonium can be decreased when it is combined with Bosentan.
IsosorbideThe serum concentration of Isosorbide can be decreased when it is combined with Bosentan.
Isosorbide DinitrateThe serum concentration of Isosorbide Dinitrate can be decreased when it is combined with Bosentan.
Isosorbide MononitrateThe serum concentration of Isosorbide Mononitrate can be decreased when it is combined with Bosentan.
IsradipineThe serum concentration of Isradipine can be decreased when it is combined with Bosentan.
ItraconazoleThe serum concentration of Itraconazole can be decreased when it is combined with Bosentan.
IvabradineThe serum concentration of Ivabradine can be decreased when it is combined with Bosentan.
IvacaftorThe serum concentration of Ivacaftor can be decreased when it is combined with Bosentan.
IxabepiloneThe serum concentration of Ixabepilone can be decreased when it is combined with Bosentan.
IxazomibThe serum concentration of Ixazomib can be decreased when it is combined with Bosentan.
KetoconazoleThe serum concentration of Ketoconazole can be decreased when it is combined with Bosentan.
LansoprazoleThe serum concentration of Lansoprazole can be decreased when it is combined with Bosentan.
LapatinibThe serum concentration of Lapatinib can be decreased when it is combined with Bosentan.
LeflunomideThe serum concentration of Bosentan can be increased when it is combined with Leflunomide.
LevonorgestrelThe serum concentration of Levonorgestrel can be decreased when it is combined with Bosentan.
LidocaineThe serum concentration of Lidocaine can be decreased when it is combined with Bosentan.
LomitapideThe serum concentration of Lomitapide can be decreased when it is combined with Bosentan.
LopinavirThe serum concentration of Bosentan can be increased when it is combined with Lopinavir.
LosartanThe serum concentration of Losartan can be decreased when it is combined with Bosentan.
LovastatinThe metabolism of Lovastatin can be increased when combined with Bosentan.
LurasidoneThe serum concentration of Lurasidone can be decreased when it is combined with Bosentan.
MacitentanThe serum concentration of MACITENTAN can be decreased when it is combined with Bosentan.
MaravirocThe serum concentration of Maraviroc can be decreased when it is combined with Bosentan.
Medroxyprogesterone acetateThe serum concentration of Medroxyprogesterone Acetate can be decreased when it is combined with Bosentan.
MefloquineThe serum concentration of Mefloquine can be decreased when it is combined with Bosentan.
MethadoneThe serum concentration of Methadone can be decreased when it is combined with Bosentan.
MidazolamThe serum concentration of Midazolam can be decreased when it is combined with Bosentan.
MifepristoneThe serum concentration of Mifepristone can be decreased when it is combined with Bosentan.
MirtazapineThe serum concentration of Mirtazapine can be decreased when it is combined with Bosentan.
ModafinilThe serum concentration of Modafinil can be decreased when it is combined with Bosentan.
NaloxegolThe serum concentration of Naloxegol can be decreased when it is combined with Bosentan.
NateglinideThe serum concentration of Nateglinide can be decreased when it is combined with Bosentan.
NefazodoneThe serum concentration of Nefazodone can be decreased when it is combined with Bosentan.
NelfinavirThe serum concentration of Bosentan can be increased when it is combined with Nelfinavir.
NevirapineThe serum concentration of Nevirapine can be decreased when it is combined with Bosentan.
NicardipineThe serum concentration of Nicardipine can be decreased when it is combined with Bosentan.
NifedipineThe serum concentration of Nifedipine can be decreased when it is combined with Bosentan.
NilotinibThe serum concentration of Nilotinib can be decreased when it is combined with Bosentan.
NimodipineThe serum concentration of Nimodipine can be decreased when it is combined with Bosentan.
NisoldipineThe serum concentration of Nisoldipine can be decreased when it is combined with Bosentan.
NorethisteroneThe serum concentration of Norethindrone can be decreased when it is combined with Bosentan.
OlaparibThe serum concentration of Olaparib can be decreased when it is combined with Bosentan.
OmeprazoleThe serum concentration of Bosentan can be increased when it is combined with Omeprazole.
OndansetronThe serum concentration of Ondansetron can be decreased when it is combined with Bosentan.
OspemifeneThe serum concentration of Ospemifene can be decreased when it is combined with Bosentan.
OxycodoneThe serum concentration of Oxycodone can be decreased when it is combined with Bosentan.
PaclitaxelThe serum concentration of Paclitaxel can be decreased when it is combined with Bosentan.
PalbociclibThe serum concentration of Palbociclib can be decreased when it is combined with Bosentan.
PanobinostatThe serum concentration of Panobinostat can be decreased when it is combined with Bosentan.
PazopanibThe serum concentration of Pazopanib can be decreased when it is combined with Bosentan.
PerampanelThe serum concentration of Perampanel can be decreased when it is combined with Bosentan.
PimozideThe serum concentration of Pimozide can be decreased when it is combined with Bosentan.
PipotiazineThe serum concentration of Pipotiazine can be decreased when it is combined with Bosentan.
PitavastatinThe metabolism of Pitavastatin can be increased when combined with Bosentan.
PosaconazoleThe serum concentration of Bosentan can be increased when it is combined with Posaconazole.
PraziquantelThe serum concentration of Praziquantel can be decreased when it is combined with Bosentan.
PrimaquineThe serum concentration of Primaquine can be decreased when it is combined with Bosentan.
ProgesteroneThe serum concentration of Progesterone can be decreased when it is combined with Bosentan.
PyrimethamineThe serum concentration of Bosentan can be increased when it is combined with Pyrimethamine.
QuetiapineThe serum concentration of Quetiapine can be decreased when it is combined with Bosentan.
QuinidineThe serum concentration of Quinidine can be decreased when it is combined with Bosentan.
QuinineThe serum concentration of Quinine can be decreased when it is combined with Bosentan.
RabeprazoleThe serum concentration of Rabeprazole can be decreased when it is combined with Bosentan.
RanolazineThe serum concentration of Ranolazine can be decreased when it is combined with Bosentan.
RegorafenibThe serum concentration of Regorafenib can be decreased when it is combined with Bosentan.
RepaglinideThe serum concentration of Repaglinide can be decreased when it is combined with Bosentan.
RifabutinThe serum concentration of Rifabutin can be decreased when it is combined with Bosentan.
RifampicinThe serum concentration of Bosentan can be decreased when it is combined with Rifampicin.
RilpivirineThe serum concentration of Rilpivirine can be decreased when it is combined with Bosentan.
RiociguatThe serum concentration of Riociguat can be decreased when it is combined with Bosentan.
RitonavirThe serum concentration of Bosentan can be increased when it is combined with Ritonavir.
RivaroxabanThe serum concentration of Rivaroxaban can be decreased when it is combined with Bosentan.
RoflumilastThe serum concentration of Roflumilast can be decreased when it is combined with Bosentan.
RolapitantThe serum concentration of Rolapitant can be decreased when it is combined with Bosentan.
RuxolitinibThe serum concentration of Ruxolitinib can be decreased when it is combined with Bosentan.
SaquinavirThe serum concentration of Saquinavir can be decreased when it is combined with Bosentan.
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Bosentan.
SildenafilThe serum concentration of Sildenafil can be decreased when it is combined with Bosentan.
SilodosinThe serum concentration of Silodosin can be decreased when it is combined with Bosentan.
SimeprevirThe serum concentration of Simeprevir can be decreased when it is combined with Bosentan.
SimvastatinThe metabolism of Simvastatin can be increased when combined with Bosentan.
SirolimusThe serum concentration of Sirolimus can be decreased when it is combined with Bosentan.
SolifenacinThe serum concentration of Solifenacin can be decreased when it is combined with Bosentan.
SonidegibThe serum concentration of Sonidegib can be decreased when it is combined with Bosentan.
SorafenibThe serum concentration of Bosentan can be increased when it is combined with Sorafenib.
SpiramycinThe serum concentration of Spiramycin can be decreased when it is combined with Bosentan.
StiripentolThe serum concentration of Stiripentol can be decreased when it is combined with Bosentan.
SulfadiazineThe serum concentration of Bosentan can be increased when it is combined with Sulfadiazine.
SulfisoxazoleThe serum concentration of Bosentan can be increased when it is combined with Sulfisoxazole.
SunitinibThe serum concentration of Sunitinib can be decreased when it is combined with Bosentan.
SuvorexantThe serum concentration of Suvorexant can be decreased when it is combined with Bosentan.
TacrolimusThe serum concentration of Tacrolimus can be decreased when it is combined with Bosentan.
TadalafilThe serum concentration of Tadalafil can be decreased when it is combined with Bosentan.
TamoxifenThe serum concentration of Tamoxifen can be decreased when it is combined with Bosentan.
TamsulosinThe serum concentration of Tamsulosin can be decreased when it is combined with Bosentan.
TasimelteonThe serum concentration of Tasimelteon can be decreased when it is combined with Bosentan.
TelaprevirThe serum concentration of Telaprevir can be decreased when it is combined with Bosentan.
TelithromycinThe serum concentration of Telithromycin can be decreased when it is combined with Bosentan.
TemsirolimusThe serum concentration of Temsirolimus can be decreased when it is combined with Bosentan.
TeniposideThe serum concentration of Teniposide can be decreased when it is combined with Bosentan.
TeriflunomideThe serum concentration of Bosentan can be increased when it is combined with Teriflunomide.
TetracyclineThe serum concentration of Tetracycline can be decreased when it is combined with Bosentan.
TheophyllineThe serum concentration of Theophylline can be decreased when it is combined with Bosentan.
TiagabineThe serum concentration of Tiagabine can be decreased when it is combined with Bosentan.
TicagrelorThe serum concentration of Ticagrelor can be decreased when it is combined with Bosentan.
TiclopidineThe serum concentration of Ticlopidine can be decreased when it is combined with Bosentan.
TipranavirThe serum concentration of Tipranavir can be decreased when it is combined with Bosentan.
TofacitinibThe serum concentration of Tofacitinib can be decreased when it is combined with Bosentan.
TolbutamideThe serum concentration of Bosentan can be increased when it is combined with Tolbutamide.
TolterodineThe serum concentration of Tolterodine can be decreased when it is combined with Bosentan.
TolvaptanThe serum concentration of Tolvaptan can be decreased when it is combined with Bosentan.
ToremifeneThe serum concentration of Toremifene can be decreased when it is combined with Bosentan.
TrabectedinThe serum concentration of Trabectedin can be decreased when it is combined with Bosentan.
TramadolThe serum concentration of Tramadol can be decreased when it is combined with Bosentan.
TrazodoneThe serum concentration of Trazodone can be decreased when it is combined with Bosentan.
TriazolamThe serum concentration of Triazolam can be decreased when it is combined with Bosentan.
TrimethoprimThe serum concentration of Trimethoprim can be decreased when it is combined with Bosentan.
TrimipramineThe serum concentration of Trimipramine can be decreased when it is combined with Bosentan.
UlipristalThe serum concentration of Ulipristal can be decreased when it is combined with Bosentan.
VandetanibThe serum concentration of Vandetanib can be decreased when it is combined with Bosentan.
VardenafilThe serum concentration of Vardenafil can be decreased when it is combined with Bosentan.
VemurafenibThe serum concentration of Vemurafenib can be decreased when it is combined with Bosentan.
VenlafaxineThe serum concentration of Venlafaxine can be decreased when it is combined with Bosentan.
VerapamilThe serum concentration of Verapamil can be decreased when it is combined with Bosentan.
VilazodoneThe serum concentration of Vilazodone can be decreased when it is combined with Bosentan.
VinblastineThe serum concentration of Vinblastine can be decreased when it is combined with Bosentan.
VincristineThe serum concentration of Vincristine can be decreased when it is combined with Bosentan.
VinorelbineThe serum concentration of Vinorelbine can be decreased when it is combined with Bosentan.
VoriconazoleThe serum concentration of Bosentan can be increased when it is combined with Voriconazole.
VortioxetineThe serum concentration of Vortioxetine can be decreased when it is combined with Bosentan.
WarfarinThe metabolism of Warfarin can be increased when combined with Bosentan.
ZafirlukastThe serum concentration of Bosentan can be increased when it is combined with Zafirlukast.
ZolpidemThe serum concentration of Zolpidem can be decreased when it is combined with Bosentan.
ZonisamideThe serum concentration of Zonisamide can be decreased when it is combined with Bosentan.
ZopicloneThe serum concentration of Zopiclone can be decreased when it is combined with Bosentan.
Food Interactions
  • Take without regard to meals.

Targets

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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Gardiner SM, Kemp PA, March JE, Bennett T: Effects of bosentan (Ro 47-0203), an ETA-, ETB-receptor antagonist, on regional haemodynamic responses to endothelins in conscious rats. Br J Pharmacol. 1994 Jul;112(3):823-30. [PubMed:7921608 ]
  3. Gupta SK, Saxena A, Singh U, Arya DS: Bosentan, the mixed ETA-ETB endothelin receptor antagonist, attenuated oxidative stress after experimental myocardial ischemia and reperfusion. Mol Cell Biochem. 2005 Jul;275(1-2):67-74. [PubMed:16335785 ]
  4. Marano G, Palazzesi S, Bernucci P, Grigioni M, Formigari R, Ballerini L: ET(A)/ET(B) receptor antagonist bosentan inhibits neointimal development in collared carotid arteries of rabbits. Life Sci. 1998;63(18):PL259-66. [PubMed:9806221 ]
  5. Richard V, Kaeffer N, Hogie M, Tron C, Blanc T, Thuillez C: Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan, a mixed ETA-ETB antagonist. Br J Pharmacol. 1994 Nov;113(3):869-76. [PubMed:7858879 ]
  6. Said SA, Ammar el SM, Suddek GM: Effect of bosentan (ETA/ETB receptor antagonist) on metabolic changes during stress and diabetes. Pharmacol Res. 2005 Feb;51(2):107-15. [PubMed:15629255 ]
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. Albertini M, Lafortuna CL, Ciminaghi B, Mazzola S, Clement MG: Endothelin involvement in respiratory centre activity. Prostaglandins Leukot Essent Fatty Acids. 2001 Sep;65(3):157-63. [PubMed:11728166 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  3. Kiowski W, Sutsch G, Oechslin E, Bertel O: Hemodynamic effects of bosentan in patients with chronic heart failure. Heart Fail Rev. 2001 Dec;6(4):325-34. [PubMed:11447307 ]
  4. Kramp R, Fourmanoir P, Caron N: Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat. Am J Physiol Renal Physiol. 2001 Dec;281(6):F1132-40. [PubMed:11704565 ]
  5. Martin C, Held HD, Uhlig S: Differential effects of the mixed ET(A)/ET(B)-receptor antagonist bosentan on endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin release. Naunyn Schmiedebergs Arch Pharmacol. 2000 Aug;362(2):128-36. [PubMed:10961375 ]
  6. Sihvola RK, Pulkkinen VP, Koskinen PK, Lemstrom KB: Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft arteriosclerosis. J Am Coll Cardiol. 2002 Feb 20;39(4):710-7. [PubMed:11849873 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinducer
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. Dingemanse J, Schaarschmidt D, van Giersbergen PL: Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clin Pharmacokinet. 2003;42(3):293-301. [PubMed:12603176 ]
  2. Dingemanse J, van Giersbergen PL: Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clin Pharmacokinet. 2004;43(15):1089-115. [PubMed:15568889 ]
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinducer
General Function:
Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Transporter activity
Specific Function:
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name:
ABCB11
Uniprot ID:
O95342
Molecular Weight:
146405.83 Da
References
  1. Fattinger K, Funk C, Pantze M, Weber C, Reichen J, Stieger B, Meier PJ: The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther. 2001 Apr;69(4):223-31. [PubMed:11309550 ]
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Drug created on June 13, 2005 07:24 / Updated on July 28, 2016 01:51