Identification

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Name
Bisoprolol
Accession Number
DB00612  (APRD00257)
Type
Small Molecule
Groups
Approved
Description

Bisoprolol is a cardioselective β1-adrenergic blocking agent used to treat high blood pressure.4,16 It is considered a potent drug with a long-half life that can be used once daily to reduce the need for multiple doses of antihypertensive drugs.4 Bisoprolol is generally well tolerated, likely due to its β1-adrenergic receptor selectivity and is a useful alternative to non-selective β-blocker drugs in the treatment of hypertension such as Carvedilol and Labetalol. It may be used alone or in combination with other drugs to manage hypertension16 and can be useful in patients with chronic obstructive pulmonary disease (COPD) due to its receptor selectivity.13

Structure
Thumb
Synonyms
  • (+-)-1-((alpha-(2-Isopropoxyethoxy)-p-tolyl)oxy)-3-(isopropylamino)-2-propanol
  • (RS)-1-(4-(2-Isopropoxyethoxymethyl)phenoxy)-3-(isopropylamino)-2-propanol
  • Bisoprolol
  • Bisoprololum
External IDs
CL 297,939 / CL 297939 / EMD 33 512 / EMD 33512
Product Ingredients
IngredientUNIICASInChI Key
Bisoprolol fumarateUR59KN573L104344-23-2VMDFASMUILANOL-WXXKFALUSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BisoprololTablet10 mgOralSorres Pharma Inc2009-02-262014-06-20Canada
BisoprololTablet5 mgOralSanis Health Inc2012-10-01Not applicableCanada
BisoprololTablet5 mgOralSorres Pharma Inc2009-02-262014-06-20Canada
BisoprololTablet10 mgOralSivem Pharmaceuticals Ulc2012-06-12Not applicableCanada
BisoprololTablet5 mgOralSivem Pharmaceuticals Ulc2012-06-12Not applicableCanada
BisoprololTablet10 mgOralSanis Health Inc2012-10-01Not applicableCanada
Monocor -(10mg)TabletOralBiovail Pharmaceuticals Canada Division Of Biovail Corporation2000-06-222005-03-10Canada
Monocor -(5mg)TabletOralBiovail Pharmaceuticals Canada Division Of Biovail Corporation2000-06-222009-07-31Canada
ZebetaTablet, film coated5 mg/1OralTeva Women's Health1993-10-202016-10-31Us51285 0060 01 nlmimage10 6838b465
ZebetaTablet, film coated10 mg/1OralTeva Women's Health1993-10-292017-05-31Us51285 0061 01 nlmimage10 a73bd3be
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-bisoprololTabletOralApotex Corporation2004-08-10Not applicableCanada
Apo-bisoprololTabletOralApotex Corporation2004-08-10Not applicableCanada
Ava-bisoprololTabletOralAvanstra Inc2011-08-222014-08-21Canada
Ava-bisoprololTabletOralAvanstra Inc2011-08-222014-08-21Canada
BisoprololTablet, film coated10 mg/1OralTrupharma, Llc2019-06-20Not applicableUs
BisoprololTablet, film coated5 mg/1OralTrupharma, Llc2019-06-20Not applicableUs
Bisoprolol FumarateTablet, film coated5 mg/1OralPhysicians Total Care, Inc.2009-08-07Not applicableUs
Bisoprolol FumarateTablet, film coated10 mg/1OralMylan Pharmaceuticals Inc.2012-09-242020-11-30Us
Bisoprolol FumarateTablet5 mg/1OralNucare Pharmaceuticals,inc.2009-09-21Not applicableUs
Bisoprolol FumarateTablet5 mg/1Oralbryant ranch prepack2009-09-212017-10-30Us63629 517320180907 15195 zpix1g
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Bisoprolol Fumarate and HydrochlorothiazideBisoprolol fumarate (10 mg/1) + Hydrochlorothiazide (6.25 mg/1)TabletOralbryant ranch prepack2010-10-122019-01-31Us
Bisoprolol Fumarate and HydrochlorothiazideBisoprolol fumarate (5 mg/1) + Hydrochlorothiazide (6.25 mg/1)TabletOralbryant ranch prepack2010-10-12Not applicableUs
Bisoprolol Fumarate and HydrochlorothiazideBisoprolol fumarate (5 mg/1) + Hydrochlorothiazide (6.25 mg/1)TabletOralAidarex Pharmaceuticals LLC2010-10-12Not applicableUs
Bisoprolol Fumarate and HydrochlorothiazideBisoprolol fumarate (5 mg/1) + Hydrochlorothiazide (6.25 mg/1)Tablet, coatedOralEon Labs, Inc.2000-09-252016-10-31Us0185 070420180907 15195 llektx
Bisoprolol Fumarate and HydrochlorothiazideBisoprolol fumarate (2.5 mg/1) + Hydrochlorothiazide (6.25 mg/1)Tablet, coatedOralMed Pharma Co., Ltd.2011-06-102012-07-11Us
Bisoprolol Fumarate and HydrochlorothiazideBisoprolol fumarate (10 mg/1) + Hydrochlorothiazide (6.25 mg/1)TabletOralREMEDYREPACK INC.2019-03-12Not applicableUs
Bisoprolol Fumarate and HydrochlorothiazideBisoprolol fumarate (5 mg/1) + Hydrochlorothiazide (6.25 mg/1)Tablet, coatedOralAv Kare, Inc.2000-03-022011-12-01Us
Bisoprolol Fumarate and HydrochlorothiazideBisoprolol fumarate (10 mg/1) + Hydrochlorothiazide (6.25 mg/1)TabletOralUnichem Pharmaceuticals (USA), Inc.2010-10-12Not applicableUs29300 0189 01 nlmimage10 3a3a9d34
Bisoprolol Fumarate and HydrochlorothiazideBisoprolol fumarate (10 mg/1) + Hydrochlorothiazide (6.25 mg/1)Tablet, coatedOralRebel Distributors2000-09-25Not applicableUs
Bisoprolol Fumarate and HydrochlorothiazideBisoprolol fumarate (2.5 mg/1) + Hydrochlorothiazide (6.25 mg/1)TabletOralRed Pharm Drug, Inc.2010-10-12Not applicableUs
International/Other Brands
Bisocor / Cardicor (Bayer) / Concor (Merck) / Concore (Merck) / Detensiel (Merck Santé) / Emconcor (Merck) / Emcor (Merck) / Euradal (Lacer) / Isoten (Meda) / Monocor (Biovail Pharmaceuticals) / Soprol (Helsinn)
Categories
UNII
Y41JS2NL6U
CAS number
66722-44-9
Weight
Average: 325.443
Monoisotopic: 325.225308485
Chemical Formula
C18H31NO4
InChI Key
VHYCDWMUTMEGQY-UHFFFAOYSA-N
InChI
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
IUPAC Name
1-[(propan-2-yl)amino]-3-(4-{[2-(propan-2-yloxy)ethoxy]methyl}phenoxy)propan-2-ol
SMILES
CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1

Pharmacology

Indication

Bisoprolol is indicated for the treatment of mild to moderate hypertension.16 It may be used off-label to treat heart failure, atrial fibrillation, and angina pectoris.1,2

Associated Conditions
Pharmacodynamics

Bisoprolol decreases heart rate (chronotropy), decreases contractility (inotropy), and reduces blood pressure.14,16 The results of various clinical studies indicate that bisoprolol reduces cardiovascular mortality and all-cause mortality in patients with heart failure and decreased cardiac ejection fraction (EF).3,8

Mechanism of action

Though the mechanism of action of bisoprolol has not been fully elucidated in hypertension, it is thought that therapeutic effects are achieved through the antagonism of β-1adrenoceptors to result in lower cardiac output. Bisoprolol is a competitive, cardioselective β1-adrenergic antagonist. When β1-receptors (located mainly in the heart)14 are activated by adrenergic neurotransmitters such as epinephrine, both the blood pressure and heart rate increase, leading to greater cardiovascular work, increasing the demand for oxygen. Bisoprolol reduces cardiac workload by decreasing contractility and the need for oxygen through competitive inhibition of β1-adrenergic receptors.7,14

Bisoprolol is also thought to reduce the output of renin in the kidneys, which normally increases blood pressure. Additionally, some central nervous system effects of bisoprolol may include diminishing sympathetic nervous system output from the brain, decreasing blood pressure and heart rate.16

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Humans
NBeta-2 adrenergic receptor
antagonist
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

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Absorption

Bisoprolol is well absorbed in the gastrointestinal tract.17 The AUC is 642.87 g.hr/mL and bioavailability of bisoprolol is about 90% due to the minimal first pass effects.1 Absorption is unaffected by food intake. Peak plasma concentrations of bisoprolol are attained within 2-4 hours and steady-state concentrations are achieved within 5 days of administration.16 In a pharmacokinetic study, the mean peak concentration of bisoprolol was 52 micrograms/L.6 Cmax at steady state concentrations of bisoprolol is 64±21 ng/ml administered at 10 mg daily.17

Volume of distribution

The volume of distribution of bisoprolol is 3.5 L/kg.17 The mean volume of distribution was found to be 230 L/kg in heart failure patients, which was similar to the volume of distribution in healthy patients.10 Bisoprolol is known to cross the placenta.15

Protein binding

Binding to serum proteins is approximately 30%.9,17

Metabolism

About 50% of a single bisoprolol dose is metabolized mainly by the enzyme CYP3A4 to inactive metabolites.16

Route of elimination

Bisoprolol is eliminated equally by both renal and hepatic pathways. About 50% of an oral dose is excreted unchanged in the urine with the remainder of the dose excreted as inactive bisoprolol metabolites. Under 2% of the ingested dose is found to be excreted in the feces.16,17

Half life

A pharmacokinetic study in 12 healthy individuals determined the mean plasma half-life of bisoprolol to be 10-12 hours.4 Another study comprised of healthy patients determined the elimination half-life to be approximately 10 hours.6 Renal impairment increased the half-life to 18.5 hours.6

Clearance

Total body clearance in healthy patients was determined to be 14.2 L/h. In patients with renal impairment, clearance was reduced to 7.8 L/h. Hepatic dysfunction also reduced the clearance of bisoprolol.6

Toxicity

LD50 information Oral LD50 of bisoprolol in the mouse was 730 mg/kg.20

Overdose information

Signs of a β-blocker overdose include cardiovascular symptoms such as hypotension, congestive heart failure, and bradycardia. Other symptoms such as bronchospasm, and hypoglycemia may occur. If an overdose occurs with bisoprolol, supportive treatment should be initiated. Glucagon has been shown to be beneficial in bradycardia and hypotension associated with beta-blocker overdosage.11 Hypoglycemia may be managed by administering IV glucose.16 Monitor the patient and administer atropine in cases of bradycardia, pressors and fluids in the case of hypotension, and conventional heart failure therapy if heart failure occurs. If heart block occurs, the patient must be closely monitored and isoproterenol infusion or transvenous cardiac pacemaker insertion should take place.16 For the management of overdose-related bronchospasm, administer bronchodilators with or without IV aminophylline. Limited research suggests that bisoprolol fumarate is not removed adequately by hemodialysis sessions.12,16

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Bisoprolol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Bisoprolol.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Bisoprolol.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid may decrease the antihypertensive activities of Bisoprolol.
1-benzylimidazole1-benzylimidazole may decrease the antihypertensive activities of Bisoprolol.
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Bisoprolol.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be increased when used in combination with Bisoprolol.
2,5-Dimethoxy-4-ethylamphetamineThe therapeutic efficacy of Bisoprolol can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe therapeutic efficacy of Bisoprolol can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
25-desacetylrifapentineThe metabolism of Bisoprolol can be increased when combined with 25-desacetylrifapentine.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Bisoprolol is combined with 3-isobutyl-1-methyl-7H-xanthine.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
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Food Interactions
  • Take without regard to meals.

References

Synthesis Reference

Yoshihiro Iwao, Katsuyuki Ookubo, Katsuhiro Okada, Kunihiro Minami, Shuichiro Yuasa, "Adhesive Pharmaceutical Preparation Containing Bisoprolol." U.S. Patent US20090169604, issued July 02, 2009.

US20090169604
General References
  1. Lancaster SG, Sorkin EM: Bisoprolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension and angina pectoris. Drugs. 1988 Sep;36(3):256-85. doi: 10.2165/00003495-198836030-00002. [PubMed:2903820]
  2. Ishiguro H, Ikeda T, Abe A, Tsukada T, Mera H, Nakamura K, Yusu S, Yoshino H: Antiarrhythmic effect of bisoprolol, a highly selective beta1-blocker, in patients with paroxysmal atrial fibrillation. Int Heart J. 2008 May;49(3):281-93. [PubMed:18612186]
  3. Metra M, Nodari S, Bordonali T, Milani P, Lombardi C, Bugatti S, Fontanella B, Verzura G, Danesi R, Dei Cas L: Bisoprolol in the treatment of chronic heart failure: from pathophysiology to clinical pharmacology and trial results. Ther Clin Risk Manag. 2007 Aug;3(4):569-78. [PubMed:18472978]
  4. Leopold G, Ungethum W, Pabst J, Simane Z, Buhring KU, Wiemann H: Pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist. Br J Clin Pharmacol. 1986 Sep;22(3):293-300. doi: 10.1111/j.1365-2125.1986.tb02890.x. [PubMed:2876722]
  5. Nuttall SL, Routledge HC, Kendall MJ: A comparison of the beta1-selectivity of three beta1-selective beta-blockers. J Clin Pharm Ther. 2003 Jun;28(3):179-86. [PubMed:12795776]
  6. Kirch W, Rose I, Demers HG, Leopold G, Pabst J, Ohnhaus EE: Pharmacokinetics of bisoprolol during repeated oral administration to healthy volunteers and patients with kidney or liver disease. Clin Pharmacokinet. 1987 Aug;13(2):110-7. doi: 10.2165/00003088-198713020-00003. [PubMed:2887325]
  7. Chatterjee SS: The cardioselective and hypotensive effects of bisoprolol in hypertensive asthmatics. J Cardiovasc Pharmacol. 1986;8 Suppl 11:S74-7. [PubMed:2439803]
  8. Dezsi CA, Szentes V: The Real Role of beta-Blockers in Daily Cardiovascular Therapy. Am J Cardiovasc Drugs. 2017 Oct;17(5):361-373. doi: 10.1007/s40256-017-0221-8. [PubMed:28357786]
  9. Leopold G: Balanced pharmacokinetics and metabolism of bisoprolol. J Cardiovasc Pharmacol. 1986;8 Suppl 11:S16-20. [PubMed:2439789]
  10. Cvan Trobec K, Grabnar I, Kerec Kos M, Vovk T, Trontelj J, Anker SD, Rosano G, Lainscak M: Bisoprolol pharmacokinetics and body composition in patients with chronic heart failure: a longitudinal study. Eur J Clin Pharmacol. 2016 Jul;72(7):813-22. doi: 10.1007/s00228-016-2041-1. Epub 2016 Mar 21. [PubMed:26996442]
  11. Peterson CD, Leeder JS, Sterner S: Glucagon therapy for beta-blocker overdose. Drug Intell Clin Pharm. 1984 May;18(5):394-8. [PubMed:6144498]
  12. Shroff GR, Herzog CA: beta-Blockers in dialysis patients: a nephrocardiology perspective. J Am Soc Nephrol. 2015 Apr;26(4):774-6. doi: 10.1681/ASN.2014080831. Epub 2014 Oct 30. [PubMed:25359873]
  13. Albouaini K, Andron M, Alahmar A, Egred M: Beta-blockers use in patients with chronic obstructive pulmonary disease and concomitant cardiovascular conditions. Int J Chron Obstruct Pulmon Dis. 2007;2(4):535-40. [PubMed:18268926]
  14. William D. Tucker; Pramod Theetha Kariyanna (2019). Selective B1 blockers. Stat Pearls Publishing.
  15. National Collaborating Centre for Women's and Children's Health (UK) (2010). NICE Guidelines for hypertension in pregnancy. RCOG Press.
  16. Bisoprolol monograph [Link]
  17. Summary of product characteristics [Link]
  18. Bisoprolol, health links AU [Link]
  19. MSDS, Bisoprolol [Link]
  20. Monograph, Bisoprolol [Link]
External Links
Human Metabolome Database
HMDB0014750
KEGG Drug
D02342
KEGG Compound
C06852
PubChem Compound
2405
PubChem Substance
46508844
ChemSpider
2312
BindingDB
25751
ChEBI
3127
ChEMBL
CHEMBL645
Therapeutic Targets Database
DAP000483
PharmGKB
PA448641
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Bisoprolol
ATC Codes
C07FX04 — Bisoprolol and acetylsalicylic acidC07BB07 — Bisoprolol and thiazidesC07AB07 — BisoprololC09BX02 — Perindopril and bisoprololC07FB07 — Bisoprolol and amlodipine
AHFS Codes
  • 24:24.00 — Beta-adrenergic Blocking Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedDiagnosticAbdominal Aortic Aneurysm Patients Under Surveillance1
0Unknown StatusPreventionPatients With Coronary Artery Disease Scheduled for by Pass Surgery1
1CompletedBasic ScienceHealthy Volunteers / Pharmacodynamics of Mirabegron1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentFasting1
1CompletedTreatmentFed1
1CompletedTreatmentHealthy Volunteers1
1WithdrawnBasic ScienceHealthy Volunteers1
1, 2Unknown StatusTreatmentIdiopathic Pulmonary Arterial Hypertension1
2TerminatedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Heart Failure1
2, 3CompletedPreventionCoronary Artery Disease / Diabetes Mellitus (DM) / Heart Failure1
2, 3RecruitingTreatmentCongestive Cardiomyopathy / Duchenne's Muscular Dystrophy (DMD)1
3CompletedTreatmentChagas Cardiomyopathy / Chronic Heart Failure (CHF)1
3CompletedTreatmentHigh Blood Pressure (Hypertension)1
3Not Yet RecruitingPreventionCardiovascular Disease (CVD) / Chronic Obstructive Pulmonary Disease (COPD)1
3RecruitingPreventionCancer, Breast / Cardiotoxicity1
4Active Not RecruitingTreatmentHypertension, Resistant to Conventional Therapy1
4CompletedHealth Services ResearchHigh Blood Pressure (Hypertension) / Metabolic Syndromes1
4CompletedPreventionAdverse Effects / Coronary Artery Atherosclerosis / Insulin resistance syndrome1
4CompletedPreventionCoronary Artery Bypass Graft Surgery Patients / Nonvalvular Atrial Fibrillation / Prevention / Prevention of Atrial Fibrillation After CABG1
4CompletedSupportive CareHigh Blood Pressure (Hypertension)1
4CompletedTreatmentBlood Pressures2
4CompletedTreatmentChronic Heart Failure (CHF)2
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)2
4CompletedTreatmentCongestive Heart Failure (CHF)1
4CompletedTreatmentHeart Failure / Ventricular Dysfunction, Left1
4CompletedTreatmentHigh Blood Pressure (Hypertension)3
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Pharmacogenetics1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedTreatmentHypertension Resistant To Conventional Therapy1
4CompletedTreatmentPostural Orthostatic Tachycardia Syndrome (POTS)1
4CompletedTreatmentUntreated Essential Hypertension1
4Not Yet RecruitingTreatmentAcute Myocardial Infarction (AMI) / Non-ST Elevation Myocardial Infarction (NSTEMI) / ST Elevation Myocardial Infarction1
4RecruitingTreatmentAcute Myocardial Infarction (AMI) / Non-ST Elevation Myocardial Infarction / ST Elevation Myocardial Infarction1
4RecruitingTreatmentHeart Diseases / Type 2 Diabetes Mellitus1
4RecruitingTreatmentHeart Failure1
4RecruitingTreatmentHigh Blood Pressure (Hypertension)1
4RecruitingTreatmentHypertension, Renal1
4RecruitingTreatmentMyocardial Infarction1
4RecruitingTreatmentPermanent Atrial Fibrillation1
4SuspendedTreatmentHeart Rate Control in ICD Patients With Heart Failure1
4TerminatedTreatmentAortic Valve Stenosis1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension)1
4Unknown StatusTreatmentStable Angina (SA)1
Not AvailableActive Not RecruitingTreatmentAcute Coronary Syndromes (ACS)1
Not AvailableActive Not RecruitingTreatmentDecompensated Heart Failure / Heart Failure With Reduced Ejection Fraction (HFrEF)1
Not AvailableCompletedNot AvailableAnesthesia; Adverse Effect / Delirium1
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)2
Not AvailableCompletedBasic ScienceArterial Hypertension / Osteopenia1
Not AvailableCompletedTreatmentChronic Heart Failure (CHF) / Nonvalvular Atrial Fibrillation1
Not AvailableCompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableCompletedTreatmentClozapine-induced Sinustachycardia1
Not AvailableCompletedTreatmentMyocardial Ischemia1
Not AvailableRecruitingNot AvailableAortic Valve Stenosis / Hypertension,Essential / Impaired Renal Function / Secondary Hypertension1
Not AvailableRecruitingNot AvailableArterial Hypertension / CHD - Coronary Heart Disease1
Not AvailableRecruitingNot AvailableHeart Failure With Reduced Ejection Fraction (HFrEF)1
Not AvailableUnknown StatusNot AvailableHeart Failure1
Not AvailableUnknown StatusTreatmentChronic Heart Failure (CHF)1

Pharmacoeconomics

Manufacturers
  • Aurobindo pharma ltd
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Unichem pharmaceuticals (usa) inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
Packagers
  • Atlantic Biologicals Corporation
  • Aurobindo Pharma Ltd.
  • Duramed
  • Eon Labs
  • Greenstone LLC
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novopharm Ltd.
  • Physicians Total Care Inc.
  • Resource Optimization and Innovation LLC
  • Teva Pharmaceutical Industries Ltd.
  • Unichem Laboratories Ltd.
  • Watson Pharmaceuticals
  • Wyeth Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral10 mg
TabletOral5 mg
TabletOral10 mg/1
TabletOral5 mg/1
Tablet, coatedOral10 mg/1
Tablet, coatedOral5 mg/1
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral5 mg/1
TabletOral
Tablet, coatedOral
Tablet, film coatedOral
TabletOral
Prices
Unit descriptionCostUnit
Condylox 0.5% Gel 3.5 gm Tube304.93USD tube
Condylox 0.5% Solution 3.5ml Bottle143.4USD bottle
Condylox 0.5% gel97.73USD g
Zebeta 10 mg tablet3.6USD tablet
Zebeta 5 mg tablet3.6USD tablet
Bisoprolol fumarate 5 mg tablet1.78USD tablet
Bisoprolol fumarate 10 mg tablet1.24USD tablet
Bisoprolol-Hydrochlorothiazide 10-6.25 mg tablet1.19USD tablet
Bisoprolol-Hydrochlorothiazide 2.5-6.25 mg tablet1.19USD tablet
Bisoprolol-Hydrochlorothiazide 5-6.25 mg tablet1.19USD tablet
Apo-Bisoprolol 10 mg Tablet0.38USD tablet
Novo-Bisoprolol 10 mg Tablet0.38USD tablet
Pms-Bisoprolol 10 mg Tablet0.38USD tablet
Sandoz Bisoprolol 10 mg Tablet0.38USD tablet
Apo-Bisoprolol 5 mg Tablet0.23USD tablet
Novo-Bisoprolol 5 mg Tablet0.23USD tablet
Pms-Bisoprolol 5 mg Tablet0.23USD tablet
Sandoz Bisoprolol 5 mg Tablet0.23USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)100-103https://www.sandoz.ca/sites/www.sandoz.ca/files/Bisoprolol_TAB_Monograph.pdf
boiling point (°C)445.0±45.0http://www.chemspider.com/Chemical-Structure.2312.html
logP2.2http://www.hmdb.ca/metabolites/HMDB0014750
logS-3.7http://www.hmdb.ca/metabolites/HMDB0014750
pKa9.5https://www.sandoz.ca/sites/www.sandoz.ca/files/Bisoprolol_TAB_Monograph.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.0707 mg/mLALOGPS
logP2.3ALOGPS
logP2.2ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area59.95 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity92.15 m3·mol-1ChemAxon
Polarizability38.5 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9445
Blood Brain Barrier-0.9077
Caco-2 permeable+0.6149
P-glycoprotein substrateSubstrate0.7785
P-glycoprotein inhibitor INon-inhibitor0.807
P-glycoprotein inhibitor IINon-inhibitor0.7821
Renal organic cation transporterNon-inhibitor0.8568
CYP450 2C9 substrateNon-substrate0.8134
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateNon-substrate0.6113
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9485
CYP450 3A4 inhibitorNon-inhibitor0.8373
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9766
Ames testNon AMES toxic0.9064
CarcinogenicityNon-carcinogens0.9267
BiodegradationNot ready biodegradable0.8962
Rat acute toxicity2.0089 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7877
hERG inhibition (predictor II)Non-inhibitor0.6611
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 , positiveLC-MS/MSsplash10-004i-0109000000-564ffde4ea3f59c4126f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-2903000000-5e5b905ef2026aa7f011
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00xr-9800000000-99ce6ca7b3171d63af09
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-9600000000-bfefc02f00a4439a34ba
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05fr-9500000000-4b91d206ced038eff35c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0ab9-9400000000-dd6baeb57f900d719aa9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0209000000-0f37dcfed3fc1c82c470
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-5902000000-dae2a435db6b3ea664cd
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05fr-9200000000-1cce569461a677bb6467
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0209000000-65dd49cd88f0ec134445
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00or-5709000000-360e67ed724045a9c01b

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzylethers
Direct Parent
Benzylethers
Alternative Parents
Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Dialkyl ethers / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Benzylether / Phenoxy compound / Phenol ether / Alkyl aryl ether / 1,2-aminoalcohol / Secondary alcohol / Dialkyl ether / Secondary amine / Secondary aliphatic amine / Ether
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
secondary alcohol, secondary amine (CHEBI:3127)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Breed JG, Ciampricotti R, Tromp GP, Valster FA, Lageweg E, Van Bortel LM: Quality of life perception during antihypertensive treatment: a comparative study of bisoprolol and enalapril. J Cardiovasc Pharmacol. 1992;20(5):750-5. [PubMed:1280737]
  2. Brouri F, Hanoun N, Mediani O, Saurini F, Hamon M, Vanhoutte PM, Lechat P: Blockade of beta 1- and desensitization of beta 2-adrenoceptors reduce isoprenaline-induced cardiac fibrosis. Eur J Pharmacol. 2004 Feb 6;485(1-3):227-34. [PubMed:14757145]
  3. Bruck H, Leineweber K, Temme T, Weber M, Heusch G, Philipp T, Brodde OE: The Arg389Gly beta1-adrenoceptor polymorphism and catecholamine effects on plasma-renin activity. J Am Coll Cardiol. 2005 Dec 6;46(11):2111-5. Epub 2005 Nov 4. [PubMed:16325050]
  4. Lipworth BJ, Irvine NA, McDevitt DG: A dose-ranging study to evaluate the beta 1-adrenoceptor selectivity of bisoprolol. Eur J Clin Pharmacol. 1991;40(2):135-9. [PubMed:1676675]
  5. Mauz AB, Pelzer H: Beta-adrenoceptor-binding studies of the cardioselective beta blockers bisoprolol, H-I 42 BS, and HX-CH 44 BS to heart membranes and intact ventricular myocytes of adult rats: two beta 1-binding sites for bisoprolol. J Cardiovasc Pharmacol. 1990 Mar;15(3):421-7. [PubMed:1691366]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
Curator comments
At higher doses, bisoprolol antagonizes the B2 receptors, but is normally selective for B1 receptors.
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Mark G. Papich (2016). Saunders Handbook of Veterinary Drugs (4th ed.). Saunders.
  2. Summary of product characteristics [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Horikiri Y, Suzuki T, Mizobe M: Pharmacokinetics and metabolism of bisoprolol enantiomers in humans. J Pharm Sci. 1998 Mar;87(3):289-94. [PubMed:9523980]
  2. Zisaki A, Miskovic L, Hatzimanikatis V: Antihypertensive drugs metabolism: an update to pharmacokinetic profiles and computational approaches. Curr Pharm Des. 2015;21(6):806-22. [PubMed:25341854]
  3. Bisoprolol monograph [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Bachmakov I, Werner U, Endress B, Auge D, Fromm MF: Characterization of beta-adrenoceptor antagonists as substrates and inhibitors of the drug transporter P-glycoprotein. Fundam Clin Pharmacol. 2006 Jun;20(3):273-82. doi: 10.1111/j.1472-8206.2006.00408.x. [PubMed:16671962]
  2. Tahara K, Kagawa Y, Takaai M, Taguchi M, Hashimoto Y: Directional transcellular transport of bisoprolol in P-glycoprotein-expressed LLC-GA5-COL150 cells, but not in renal epithelial LLC-PK1 Cells. Drug Metab Pharmacokinet. 2008;23(5):340-6. [PubMed:18974611]
  3. Nehaj F, Sokol J, Ivankova J, Mokan M, Mokan M: Effect of Bisoprolol on the Level of Dabigatran. Am J Ther. 2018 Jul 12. doi: 10.1097/MJT.0000000000000786. [PubMed:30074534]
  4. Klatt S, Fromm MF, Konig J: Transporter-mediated drug-drug interactions with oral antidiabetic drugs. Pharmaceutics. 2011 Oct 12;3(4):680-705. doi: 10.3390/pharmaceutics3040680. [PubMed:24309303]

Drug created on June 13, 2005 07:24 / Updated on September 17, 2019 03:38