BISOPROLOL

Details

Stereochemistry	RACEMIC
Molecular Formula	C18H31NO4
Molecular Weight	325.443
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1

InChI

InChIKey=VHYCDWMUTMEGQY-UHFFFAOYSA-N

InChI=1S/C18H31NO4/c1-14(2)19-11-17(20)13-23-18-7-5-16(6-8-18)12-21-9-10-22-15(3)4/h5-8,14-15,17,19-20H,9-13H2,1-4H3

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020186s027s028lbl.pdf
Curator's Comment: description was created based on several sources, including: http://www.healthline.com/drugs/bisoprolol/oral-tablet#Highlights1 https://www.drugs.com/ppa/bisoprolol.html http://pharm-sci.tbzmed.ac.ir/Drug-Information/Integrative%20Medicine%20Professional%20Access/ProfDrugs/Bisoprololpd.html http://www.drugbank.ca/drugs/DB00612 https://en.wikipedia.org/wiki/Bisoprolol

Bisoprolol is a cardioselective beta1-adrenergic blocking agent. It lower the heart rate and blood pressure and may be used to reduce workload on the heart and hence oxygen demands. This results in a reduction of heart rate, cardiac output, systolic and diastolic blood pressure, and possibly reflex orthostatic hypotension. Bisoprolol can be used to treat cardiovascular diseases such as hypertension, coronary heart disease, arrhythmias, ischemic heart diseases, and myocardial infarction after the acute event. General side effects are: fatigue, asthenia, chest pain, malaise, edema, weight gain, angioedema. Concurrent use of rifampin increases the metabolic clearance of bisoprolol fumarate, shortening its elimination half-life.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Beta-1 adrenergic receptor 158 Target ID: CHEMBL213 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020186s027s028lbl.pdf	Blocker 534	8.8 nM [IC50]
Cytochrome P450 2D6 61 Target ID: CHEMBL289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9523980	Substrate 656
Cytochrome P450 3A4 126 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9523980	Substrate 656

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 549 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020186s027s028lbl.pdf	Primary		Approved 8360	ZIAC Approved Use BISOPROLOL FUMARATE is indicated in the management of hypertension. It may be used alone or in combination with other antihypertensive agents. Launch Date 7.330176E11

C_max

Value	Dose	Co-administered	Analyte	Population
52 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2887325/	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		BISOPROLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
40.37 ng/mL DRUG LABEL https://www.sandoz.ca/sites/www.sandoz.ca/files/Bisoprolol_TAB_Monograph.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		BISOPROLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
661 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2887325/	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		BISOPROLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
609.8 ng × h/mL DRUG LABEL https://www.sandoz.ca/sites/www.sandoz.ca/files/Bisoprolol_TAB_Monograph.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		BISOPROLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
10 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2887325/	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		BISOPROLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
11.07 h DRUG LABEL https://www.sandoz.ca/sites/www.sandoz.ca/files/Bisoprolol_TAB_Monograph.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		BISOPROLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
70% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2887325/	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		BISOPROLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
70% DRUG LABEL https://www.sandoz.ca/sites/www.sandoz.ca/files/Bisoprolol_TAB_Monograph.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		BISOPROLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
10 mg single, oral Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2897298/	unhealthy, 37 - 52 years n = 15 Health Status: unhealthy Condition: liver disease Age Group: 37 - 52 years Sex: M+F Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/2897298/	Other AEs: Dizziness, Tiredness... Other AEs: Dizziness (2 patients) Tiredness (1 patient) Shortness of breath (1 patient) Faintness (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/2897298/
10 mg 1 times / day steady, oral (max) Highest studied dose Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10023943/	unhealthy, adult n = 1327 Health Status: unhealthy Condition: heart failure Age Group: adult Sex: unknown Population Size: 1327 Sources: https://pubmed.ncbi.nlm.nih.gov/10023943/	Sources: https://pubmed.ncbi.nlm.nih.gov/10023943/
5 mg 1 times / day steady, intravenous (max) Highest studied dose Dose: 5 mg, 1 times / day Route: intravenous Route: steady Dose: 5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11527129/	unhealthy, adult n = 37 Health Status: unhealthy Condition: myocardial infarction Age Group: adult Sex: unknown Population Size: 37 Sources: https://pubmed.ncbi.nlm.nih.gov/11527129/	Sources: https://pubmed.ncbi.nlm.nih.gov/11527129/
20 mg 1 times / day steady, oral (max) Recommended Dose: 20 mg, 1 times / day Route: oral Route: steady Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf	unhealthy, adult n = 273 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: unknown Population Size: 273 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf	Other AEs: Sweating increased, Arthralgia... Other AEs: Sweating increased (0.7%) Arthralgia (2.2%) Dizziness (2.9%) Headache (8.8%) Hypoaesthesia (1.1%) Dry mouth (0.7%) Bradycardia (0.4%) Insomnia (1.5%) Diarrhea (2.6%) Nausea (1.5%) Vomiting (1.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf
20 mg 1 times / day steady, oral (max) Recommended Dose: 20 mg, 1 times / day Route: oral Route: steady Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf	unhealthy, adult n = 273 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: unknown Population Size: 273 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf	Disc. AE: Bradycardia, Fatigue... AEs leading to discontinuation/dose reduction: Bradycardia (< 1%) Fatigue (< 1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf
40 mg 1 times / day steady, oral (max) Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf	unhealthy, adult n = 404 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: unknown Population Size: 404 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf	Other AEs: Headache, Hypoaesthesia... Other AEs: Headache (10.9%) Hypoaesthesia (1.5%) Sweating increased (1%) Arthralgia (2.7%) Dizziness (3.5%) Dry mouth (1.3%) Bradycardia (0.5%) Insomnia (2.5%) Depression (0.2%) Diarrhea (3.5%) Nausea (2.2%) Vomiting (1.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf
40 mg 1 times / day steady, oral (max) Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf	unhealthy, adult n = 404 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: unknown Population Size: 404 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf	Disc. AE: Bradycardia, Fatigue... AEs leading to discontinuation/dose reduction: Bradycardia (< 1%) Fatigue (< 1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019982s014lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709		substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1437 OCT2 638 OCT1 506 OCT3 149 OCTN1 29 OCTN2 66	P-gp 1527

Drug as perpetrator

Target	Modality	Activity
OCT3 149	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/21641380/	no
OCTN1 29	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/21641380/	no
OCTN2 71	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/21641380/	no
OCT2 639	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19740083/	yes [IC50 2.4 uM]
OCT1 523	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/21641380/	yes
P-gp 1626	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16671962/	yes

Drug as victim

Target	Modality	Activity
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9523980/	yes
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9523980/	yes
P-gp 1527	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/18974611/ \| https://pubmed.ncbi.nlm.nih.gov/16671962/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3127	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3127
ChemicalBook	CB03118896	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB03118896
ChemicalBook	CB13118893	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB13118893
ChemicalBook	CB33118897	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB33118897
ChemicalBook	CB73118895	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB73118895
ChemicalBook	CB83118892	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB83118892
MolPort	MolPort-003-666-876	https://www.molport.com/shop/molecule-link/MolPort-003-666-876
MolPort	MolPort-005-937-320	https://www.molport.com/shop/molecule-link/MolPort-005-937-320
eMolecules	901481	https://www.emolecules.com/cgi-bin/more?vid=901481

PubMed

Title	Date	PubMed
[Treatment of cardiac insufficiency: does treatment depend on whether its cause is ischemic or idiopathic?].	1999 Jun	10410811
Prevention of experimental autoimmune cardiomyopathy in rabbits by receptor blockers.	2001	11908781
Cost effectiveness of bisoprolol in the treatment of chronic congestive heart failure in Sweden: analysis using data from the Cardiac Insufficiency Bisoprolol Study II trial.	2001	11700777
[Clinical trials on heart failure].	2001	11535185
Quantitative structure-retention and retention-activity relationships of beta-blocking agents by micellar liquid chromatography.	2001 Apr 6	11330791
Results from post-hoc analyses of the CIBIS II trial: effect of bisoprolol in high-risk patient groups with chronic heart failure.	2001 Aug	11511434
Predictors of medical events and of their competitive interactions in the Cardiac Insufficiency Bisoprolol Study 2 (CIBIS-2).	2001 Dec	11717602
Immunofluorescent imaging of beta 1- and beta 2-adrenergic receptors in rat kidney.	2001 Feb	11168934
[A must in symptomatic heart failure. Added beta blocker improves prognosis].	2001 Feb 1	11234521
[Bisprolol in heart failure: efficacy and costs in a French setting according to CIBIS II].	2001 Jul-Aug	11677866
Beta-blockers to reduce mortality in patients with systolic dysfunction: a meta-analysis.	2001 Jun	11401736
[Hypertensive diabetic patients. Plus points for selective beta 1-blockade].	2001 Jun 7	11460423
Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial.	2001 Mar 13	11245648
Autoimmunity against the second extracellular loop of beta(1)-adrenergic receptors induces beta-adrenergic receptor desensitization and myocardial hypertrophy in vivo.	2001 Mar 30	11282891
The effects of bisoprolol, a selective beta1-blocker, on glucose metabolism by long-term administration in essential hypertension.	2001 May	11349822
Carvedilol in the treatment of chronic heart failure.	2001 May	11336626
Economic impact of beta blockade in heart failure.	2001 May 7	11334781
Renin-angiotensin system is involved in the mechanism of increased serum asymmetric dimethylarginine in essential hypertension.	2001 Sep	11548874
[Role of beta-blockers in the treatment of chronic heart heart failure].	2001 Sep 16	11582731
Bisoprolol: a review of its use in chronic heart failure.	2002	12466013
Optimising the use of beta-blockers in older patients with heart failure.	2002	12381236
[The effect of aspirin on rheological properties of erythrocytes in essential hypertension].	2002	12152252
Differential effects of bucindolol and carvedilol on noradenaline-induced hypertrophic response in ventricular cardiomyocytes of adult rats.	2002 Apr	11907159
Beta-blockers work as well in women as in men.	2002 Apr 5	12452171
[Hormonal hyperactivity in heart failure. Differences in beta blockers].	2002 Aug	12229258
Bisoprolol for the treatment of chronic heart failure: a meta-analysis on individual data of two placebo-controlled studies--CIBIS and CIBIS II. Cardiac Insufficiency Bisoprolol Study.	2002 Feb	11835035
Can beta blockers be safely initiated at home in patients with heart failure?	2002 Jan	11834774
Comparison of the affinity of beta-blockers for two states of the beta 1-adrenoceptor in ferret ventricular myocardium.	2002 Jan	11815381
[Therapy relevant differences in beta blockers and ACE inhibitors. Innovation or plagiarism?].	2002 Jan 17	11847884
Present and future pharmacotherapy for heart failure.	2002 Jul	12083991
[Heart failure. Only every fifth patient is properly treated?].	2002 Jun 20	12136677
Beta-blocker decreases the increase in QT dispersion and transmural dispersion of repolarization induced by bepridil.	2002 Nov	12419934
Functional beta1- and beta2-adrenoceptors in the left and right atrium of pre-hypertensive rats.	2002 Oct	12396304
[Beta blockers in heart failure. Start with low and slowly increase the dosage!].	2002 Sep 19	12395713
Storms of ventricular tachyarrhythmias associated with primary hyperparathyroidism in a patient with dilated cardiomyopathy.	2003 Jan	12468064

Patents

Sample Use Guides

In Vivo Use Guide

2.5 to 40 mg once-daily dose

Route of Administration: Oral

In Vitro Use Guide

Positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) test and in the mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide of 43-1300 µg/mL.

Name

Type

Language

BISOPROLOL

Official Name

English

BISOPROLOL [USAN]

Common Name

English

BISOPROLOL [VANDF]

Common Name

English

BISOPROLOL [MI]

Common Name

English

2-PROPANOL, 1-(4-((2-(1-METHYLETHOXY)ETHOXY)METHYL)PHENOXY)-3-((1-METHYLETHYL)AMINO)-, (±)-

Systematic Name

English

(±)-1-((.ALPHA.-(2-ISOPROPOXYETHOXY)-P-TOLYL)OXY)-3-(ISOPROPYLAMINO)-2-PROPANOL

Common Name

English

EMD 33 512

Code

English

BISOPROLOL [JAN]

Common Name

English

bisoprolol [INN]

Common Name

English

Bisoprolol [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC07BB07