Identification

Name
Bosentan
Accession Number
DB00559  (APRD00829)
Type
Small Molecule
Groups
Approved, 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
  • bosentan anhydrous
  • bosentanum
  • p-tert-Butyl-N-(6-(2-hydroxyethoxy)-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl)benzenesulfonamide
Product Ingredients
IngredientUNIICASInChI Key
Bosentan monohydrateQ326023R30157212-55-0SXTRWVVIEPWAKM-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act BosentanTablet125 mgOralActavis Pharma Company2012-06-05Not applicableCanada
Act BosentanTablet62.5 mgOralActavis Pharma Company2012-06-05Not applicableCanada
BosentanTablet62.5 mgOralActelionNot applicableNot applicableCanada
BosentanTablet125 mgOralPanda Pharmaceuticals Inc.Not applicableNot applicableCanada
BosentanTablet125 mgOralActelionNot applicableNot applicableCanada
BosentanTablet62.5 mgOralPanda Pharmaceuticals Inc.Not applicableNot applicableCanada
Bosentan TabletsTablet125 mgOralAccord Healthcare Limited2014-11-132015-06-02Canada
Sandoz BosentanTablet62.5 mgOralSandoz Canada Incorporated2012-06-13Not applicableCanada
Sandoz BosentanTablet125 mgOralSandoz Canada Incorporated2012-06-13Not applicableCanada
StayveerTablet, film coated62.5 mgOralMarklas Nederlands Bv2013-06-24Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel-bosentanTablet125 mgOralAccel Pharma IncNot applicableNot applicableCanada
Apo-bosentanTablet125.0 mgOralApotex Corporation2017-07-14Not applicableCanada
Apo-bosentanTablet62.5 mgOralApotex Corporation2017-07-14Not applicableCanada
Bio-bosentanTablet125 mgOralBiomed Pharma2017-08-23Not applicableCanada
Bio-bosentanTablet62.5 mgOralBiomed Pharma2017-08-23Not applicableCanada
Ipg-bosentanTablet125 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Ipg-bosentanTablet62.5 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Mar-bosentanTablet125 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Mar-bosentanTablet62.5 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Mylan-bosentanTablet125.0 mgOralMylan Pharmaceuticals2012-05-29Not applicableCanada
Categories
UNII
XUL93R30K2
CAS number
147536-97-8
Weight
Average: 551.614
Monoisotopic: 551.183854375
Chemical Formula
C27H29N5O6S
InChI Key
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

Pharmacology

Indication

Used 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).

Associated Conditions
Pharmacodynamics

Bosentan 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 action

Endothelin-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.

TargetActionsOrganism
AEndothelin-1 receptor
antagonist
Human
AEndothelin B receptor
antagonist
Human
Absorption

Absolute bioavailability is approximately 50% and food does not affect absorption.

Volume of distribution
  • 18 L
Protein binding

Greater 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.

Route of elimination

Bosentan is eliminated by biliary excretion following metabolism in the liver.

Half life

Terminal elimination half-life is about 5 hours in healthy adult subjects.

Clearance
  • 4 L/h [patients with pulmonary arterial hypertension]
Toxicity

Bosentan 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Bosentan.
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Bosentan.
AbirateroneThe serum concentration of Bosentan can be increased when it is combined with Abiraterone.
AcebutololBosentan may increase the hypotensive activities of Acebutolol.
AcemetacinThe therapeutic efficacy of Bosentan can be decreased when used in combination with Acemetacin.
AcenocoumarolThe serum concentration of Acenocoumarol can be decreased when it is combined with Bosentan.
AcetaminophenThe serum concentration of Acetaminophen can be decreased when it is combined with Bosentan.
Acetyl sulfisoxazoleThe serum concentration of Bosentan can be increased when it is combined with Acetyl sulfisoxazole.
Acetylsalicylic acidThe therapeutic efficacy of Bosentan can be decreased when used in combination with Acetylsalicylic acid.
AdinazolamThe serum concentration of Adinazolam can be decreased when it is combined with Bosentan.
Food Interactions
  • Take without regard to meals.

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 References
Not Available
External Links
Human Metabolome Database
HMDB0014699
KEGG Drug
D01227
PubChem Compound
104865
PubChem Substance
46507154
ChemSpider
94651
BindingDB
50061101
ChEBI
51450
ChEMBL
CHEMBL957
Therapeutic Targets Database
DNC000341
PharmGKB
PA10034
HET
K86
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Bosentan
ATC Codes
C02KX01 — Bosentan
AHFS Codes
  • 48:48.00 — Vasodilating Agents
PDB Entries
5xpr
FDA label
Download (424 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic SciencePulmonary Arterial Hypertension (PAH) / Vasoconstriction / Vasodilation1
1CompletedTreatmentAltitude / Pulmonary Hypertension (PH)1
1CompletedTreatmentBioequivalence Study / Pulmonary Arterial Hypertension (PAH)1
1CompletedTreatmentBlood Flow Velocity / Glaucoma1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHigh Blood Pressure (Hypertension)1
1CompletedTreatmentHypoxia-Induced Pulmonary Artery Hypertension1
1Unknown StatusTreatmentHealthy Volunteers1
1, 2TerminatedTreatmentSystemic Sclerosis (Scleroderma)1
1, 2Unknown StatusTreatmentChildhood rheumatoid fever / Congestive Heart Failure (CHF) / Mitral Valve Stenosis / Pulmonary Hypertension Secondary1
2Active Not RecruitingTreatmentCongenital Heart Disease (CHD) / Pulmonary Arterial Hypertension (PAH)1
2CompletedTreatmentDefect, Congenital Heart / Functional Single Ventricle1
2CompletedTreatmentHand Functionality / Scleroderma, Systemic / Skin Fibrosis1
2CompletedTreatmentHigh Blood Pressure (Hypertension) / Obstructive Sleep Apnea (OSA)1
2CompletedTreatmentHypoplastic Left Heart Syndrome (HLHS) / Other Specified Congenital Anomalies of Heart / Tricuspid Atresia1
2CompletedTreatmentMelanoma1
2CompletedTreatmentPort-wine Stains (PWS)1
2CompletedTreatmentScleroderma Renal Crisis1
2CompletedTreatmentType 2 Diabetes Mellitus1
2TerminatedTreatmentAsthma Bronchial1
2TerminatedTreatmentHepatopulmonary Syndrome / Liver Cirrhosis1
2TerminatedTreatmentPulmonary Hypertension (PH) / Sarcoidosis1
2TerminatedTreatmentPulmonary Hypertension (PH) / Scleroderma, Systemic1
2Unknown StatusTreatmentAsthma Bronchial1
2Unknown StatusTreatmentChronic Obstructive Pulmonary Disease (COPD)1
2, 3CompletedBasic SciencePulmonary Hypertension (PH)1
2, 3CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
2, 3CompletedTreatmentInterstitial Lung Disease (ILD) / Scleroderma1
2, 3CompletedTreatmentPulmonary Arterial Hypertension (PAH) / Sarcoidosis1
2, 3CompletedTreatmentPulmonary Fibrosis / Scleroderma, Systemic1
3CompletedTreatmentChronic Thromboembolic Pulmonary Hypertension1
3CompletedTreatmentDigital Ulcers / Scleroderma / Sclerosis, Progressive Systemic1
3CompletedTreatmentDigital Ulcers / Sclerosis, Progressive Systemic1
3CompletedTreatmentEisenmenger's Syndrome1
3CompletedTreatmentHeart Failure, Diastolic / Pulmonary Hypertension (PH)1
3CompletedTreatmentHeart Septal Defects, Atrial1
3CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)2
3CompletedTreatmentPulmonary Arterial Hypertension (PAH)2
3CompletedTreatmentPulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH)2
3CompletedTreatmentPulmonary Hypertension (PH)2
3RecruitingTreatmentIschemic Optic Neuropathy1
3TerminatedTreatmentPersistent Pulmonary Hypertension of the Newborn1
3TerminatedTreatmentPulmonary Hypertension (PH)3
3TerminatedTreatmentPulmonary Hypertension (PH) / Sickle Cell Disorders1
3TerminatedTreatmentType 2 Diabetes Mellitus1
3Unknown StatusTreatmentConnective Tissue Diseases / Pulmonary Hypertension (PH)1
3Unknown StatusTreatmentPulmonary Arterial Hypertension (PAH)1
4Active Not RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
4CompletedBasic ScienceType 2 Diabetes Mellitus1
4CompletedSupportive CareType 2 Diabetes Mellitus1
4CompletedTreatmentDigital Ulcers / Sclerosis, Progressive Systemic1
4CompletedTreatmentEisenmenger's Syndrome1
4CompletedTreatmentPulmonary Arterial Hypertension (PAH)4
4CompletedTreatmentPulmonary Arterial Hypertension Related to Eisenmenger Physiology1
4CompletedTreatmentPulmonary Hypertension (PH)2
4Not Yet RecruitingTreatmentScleroderma, Systemic1
4RecruitingTreatmentAssociated Pulmonary Arterial Hypertension1
4TerminatedNot AvailablePulmonary Hypertension (PH)1
4TerminatedTreatmentPulmonary Hypertension (PH)1
4Unknown StatusTreatmentIdiopathic Pulmonary Fibrosis (IPF) / Interstitial Lung Disease (ILD) / Nonspecific Interstitial Pneumonia / Pulmonary Hypertension (PH)1
4Unknown StatusTreatmentPulmonary Hypertension Secondary to Lung Disease and/or Hypoxia1
4WithdrawnTreatmentIdiopathic Pulmonary Fibrosis (IPF) / Pulmonary Arterial Hypertension (PAH)1
Not AvailableCompletedNot AvailablePulmonary Arterial Hypertension (PAH)1
Not AvailableCompletedNot AvailableThromboangiitis Obliterans1
Not AvailableCompletedNot AvailableVA Drug Interactions [VA Drug Interaction]1
Not AvailableCompletedSupportive CareCongenital Heart Disease (CHD)1
Not AvailableCompletedTreatmentPeripheral Arterial Disease (PAD)1
Not AvailableCompletedTreatmentPulmonary Arterial Hypertension (PAH)1
Not AvailableCompletedTreatmentPulmonary Hypertension (PH) / Sclerosis, Progressive Systemic1
Not AvailableRecruitingTreatmentCongenital Heart Disease (CHD)1
Not AvailableRecruitingTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableUnknown StatusNot AvailablePAH WHO Group I / Pulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH)1
Not AvailableUnknown StatusPreventionRaynaud's Phenomenon / Skin Necrosis1

Pharmacoeconomics

Manufacturers
  • Actelion ltd
Packagers
  • Actelion Pharmaceuticals Inc.
  • Action Pharmaceuticals Ltd.
  • Haupt Pharma
  • Patheon Inc.
Dosage forms
FormRouteStrength
TabletOral125.0 mg
Tablet, film coatedOral125 mg
Tablet, film coatedOral62.5 mg
TabletOral125 mg
TabletOral62.5 mg
Tablet, film coatedOral125 mg/1
Tablet, film coatedOral62.5 mg/1
Tablet, for suspensionOral32 mg
Tablet, solubleOral32 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2071193No1998-08-252012-06-12Canada
US5292740No1995-11-202015-11-20Us
US7959945No2007-12-282027-12-28Us
US8309126No2006-05-152026-05-15Us

Properties

State
Solid
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udj-0810090000-b97444dff91ec725276d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-1690040000-c561d9dbb5ed88285519

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Bipyrimidines and oligopyrimidines
Alternative Parents
Diarylethers / Benzenesulfonamides / Phenylpropanes / Benzenesulfonyl compounds / Phenoxy compounds / Anisoles / Methoxybenzenes / Alkyl aryl ethers / Organosulfonamides / Imidolactams
show 8 more
Substituents
Bipyrimidine / Diaryl ether / Benzenesulfonamide / Benzenesulfonyl group / Phenylpropane / Phenoxy compound / Anisole / Phenol ether / Methoxybenzene / Alkyl aryl ether
show 22 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
sulfonamide, pyrimidines, primary alcohol (CHEBI:51450)

Targets

Details
1. Endothelin-1 receptor
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:...
Gene Name
EDNRA
Uniprot ID
P25101
Uniprot Name
Endothelin-1 receptor
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]
Details
2. Endothelin B receptor
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
Uniprot Name
Endothelin B receptor
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]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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
Substrate
Inducer
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
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
Uniprot Name
Bile salt export pump
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]

Drug created on June 13, 2005 07:24 / Updated on September 21, 2018 00:02