General Information of Drug (ID: DM3UZ95)

Drug Name
Bisoprolol
Synonyms
Bisocor; Bisoprololum; Cardicor; Concor; Detensiel; Emconcor; Emcor; Euradal; Isoten; Monocor; Soloc; Soprol; Zebeta; Bisoprolol fumerate; Bisoprolol hemifumarate; Bisoprololum [Latin]; CL-297939; Concor (TN); Concore (TN); EMD-33512; Monocor (TN); Zebeta (TN); Bisoprolol (USAN/INN); Bisoprolol [USAN:BAN:INN]; EMD-33-512; (+-)-1-((alpha-(2-Isopropoxyethoxy)-p-tolyl)oxy)-3-(isopropylamino)-2-propanol; (RS)-1-(4-(2-Isopropoxyethoxymethyl)phenoxy)-3-(isopropylamino)-2-propanol; 1-(propan-2-ylamino)-3-[4-(2-propan-2-yloxyethoxymethyl)phenoxy]propan-2-ol; 1-[(1-methylethyl)amino]-3-({4-[({2-[(1-methylethyl)oxy]ethyl}oxy)methyl]phenyl}oxy)propan-2-ol; 1-{4-[(2-isopropoxyethoxy)methyl]phenoxy}-3-(isopropylamino)propan-2-ol
Indication
Disease Entry ICD 11 Status REF
Hypertension BA00-BA04 Approved [1]
Malignant essential hypertension BA00 Approved [2]
Therapeutic Class
Antihypertensive Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 325.4
Logarithm of the Partition Coefficient (xlogp) 1.9
Rotatable Bond Count (rotbonds) 12
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2 h []
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
Bioavailability
The bioavailability of drug is 95% []
Clearance
The total body clearance of drug is 14.2 L/h [4]
Elimination
About 50% of an oral dose is excreted unchanged in the urine with the remainder of the dose excreted as inactive bisoprolol metabolites [5]
Half-life
The concentration or amount of drug in body reduced by one-half in 10 - 12 hours (in healthy individuals) [6]
Metabolism
The drug is metabolized via the cytochrome P450 enzym CYP3A4 to inactive metabolites [5]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.877 micromolar/kg/day [7]
Unbound Fraction
The unbound fraction of drug in plasma is 0.66% [8]
Vd
The volume of distribution (Vd) of drug is 3.5 L/kg [9]
Adverse Drug Reaction (ADR)
ADR Term Variation Related DOT DOT ID REF
Adverse drug reaction Not Available CYP2D6 OTZJC802 [10]
Chemical Identifiers
Formula
C18H31NO4
IUPAC Name
1-(propan-2-ylamino)-3-[4-(2-propan-2-yloxyethoxymethyl)phenoxy]propan-2-ol
Canonical SMILES
CC(C)NCC(COC1=CC=C(C=C1)COCCOC(C)C)O
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
InChIKey
VHYCDWMUTMEGQY-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
2405
ChEBI ID
CHEBI:3127
CAS Number
66722-44-9
DrugBank ID
DB00612
TTD ID
D0K3ZR
INTEDE ID
DR0216
ACDINA ID
D00072
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Adrenergic receptor beta-1 (ADRB1) TTR6W5O ADRB1_HUMAN Antagonist [11]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME
DE4LYSA CP3A4_HUMAN Substrate [12]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [13]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Regulation of Drug Effects [14]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Gene/Protein Processing [15]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Drug Response [10]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Gene/Protein Processing [15]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Gene/Protein Processing [15]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Gene/Protein Processing [15]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Gene/Protein Processing [15]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Bisoprolol
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Levamlodipine DM92S6N Moderate Increased risk of cardiac depression by the combination of Bisoprolol and Levamlodipine. Hypertension [BA00-BA04] [16]
Verapamil DMA7PEW Major Increased risk of cardiac depression by the combination of Bisoprolol and Verapamil. Hypertension [BA00-BA04] [16]
Indapamide DMGN1PW Moderate Increased risk of hyperglycemia by the combination of Bisoprolol and Indapamide. Hypertension [BA00-BA04] [17]
Trichlormethiazide DMHAQCO Moderate Increased risk of hypertriglyceridemia by the combination of Bisoprolol and Trichlormethiazide. Hypertension [BA00-BA04] [17]
Hydrochlorothiazide DMUSZHD Moderate Increased risk of ventricular arrhythmias by the combination of Bisoprolol and Hydrochlorothiazide. Hypertension [BA00-BA04] [17]
Clevidipine butyrate DMW4M97 Moderate Increased risk of cardiac depression by the combination of Bisoprolol and Clevidipine butyrate. Hypertension [BA00-BA04] [16]
⏷ Show the Full List of 6 DDI Information of This Drug
Coadministration of a Drug Treating the Disease Different from Bisoprolol (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Scopolamine DMOM8AL Moderate Antagonize the effect of Bisoprolol when combined with Scopolamine. Addictive disorder [6C50-6C5Z] [18]
Bepridil DM0RKS4 Moderate Increased risk of cardiac depression by the combination of Bisoprolol and Bepridil. Angina pectoris [BA40] [16]
Dronedarone DMA8FS5 Moderate Increased risk of atrioventricular block by the combination of Bisoprolol and Dronedarone. Angina pectoris [BA40] [19]
Nifedipine DMSVOZT Moderate Increased risk of cardiac depression by the combination of Bisoprolol and Nifedipine. Angina pectoris [BA40] [16]
Zileuton DMVRIC2 Moderate Decreased metabolism of Bisoprolol caused by Zileuton. Asthma [CA23] [20]
Cariprazine DMJYDVK Moderate Additive hypotensive effects by the combination of Bisoprolol and Cariprazine. Bipolar disorder [6A60] [21]
Atracurium DM42HXN Moderate Additive neuromuscular blocking effects by the combination of Bisoprolol and Atracurium. Corneal disease [9A76-9A78] [22]
Mivacurium DM473VD Moderate Additive neuromuscular blocking effects by the combination of Bisoprolol and Mivacurium. Corneal disease [9A76-9A78] [22]
Tubocurarine DMBZIVP Moderate Additive neuromuscular blocking effects by the combination of Bisoprolol and Tubocurarine. Corneal disease [9A76-9A78] [22]
Pasireotide DMHM7JS Moderate Increased risk of bradycardia by the combination of Bisoprolol and Pasireotide. Cushing syndrome [5A70] [23]
OPC-34712 DMHG57U Moderate Additive hypotensive effects by the combination of Bisoprolol and OPC-34712. Depression [6A70-6A7Z] [21]
Mepenzolate DM8YU2F Moderate Antagonize the effect of Bisoprolol when combined with Mepenzolate. Digestive system disease [DE2Z] [18]
Oxybutynine DMJPBAX Moderate Antagonize the effect of Bisoprolol when combined with Oxybutynine. Discovery agent [N.A.] [18]
Ethacrynic acid DM60QMR Moderate Increased risk of hyperglycemia by the combination of Bisoprolol and Ethacrynic acid. Essential hypertension [BA00] [17]
Phenoxybenzamine DM8KSQH Moderate Additive hypotensive effects by the combination of Bisoprolol and Phenoxybenzamine. Essential hypertension [BA00] [24]
Nicardipine DMCDYW7 Moderate Increased risk of cardiac depression by the combination of Bisoprolol and Nicardipine. Essential hypertension [BA00] [16]
Tolterodine DMSHPW8 Moderate Antagonize the effect of Bisoprolol when combined with Tolterodine. Functional bladder disorder [GC50] [18]
Propantheline DM2EN6G Moderate Antagonize the effect of Bisoprolol when combined with Propantheline. Gastric ulcer [DA60] [18]
Chlorothiazide DMLHESP Moderate Increased risk of hypertriglyceridemia by the combination of Bisoprolol and Chlorothiazide. Heart failure [BD10-BD1Z] [17]
Furosemide DMMQ8ZG Moderate Increased risk of hyperglycemia by the combination of Bisoprolol and Furosemide. Heart failure [BD10-BD1Z] [17]
Bumetanide DMRV7H0 Moderate Increased risk of ventricular arrhythmias by the combination of Bisoprolol and Bumetanide. Heart failure [BD10-BD1Z] [17]
Hydroflumethiazide DMVPUQI Moderate Increased risk of hyperglycemia by the combination of Bisoprolol and Hydroflumethiazide. Heart failure [BD10-BD1Z] [17]
Rifampin DMA8J1G Moderate Increased metabolism of Bisoprolol caused by Rifampin mediated induction of CYP450 enzyme. HIV-infected patients with tuberculosis [1B10-1B14] [25]
Belladonna DM2RBWK Moderate Antagonize the effect of Bisoprolol when combined with Belladonna. Infectious gastroenteritis/colitis [1A40] [18]
Propiomazine DMKY8V1 Moderate Additive hypotensive effects by the combination of Bisoprolol and Propiomazine. Insomnia [7A00-7A0Z] [21]
ITI-007 DMUQ1DO Moderate Additive hypotensive effects by the combination of Bisoprolol and ITI-007. Insomnia [7A00-7A0Z] [21]
Clidinium DMUMQZ0 Moderate Antagonize the effect of Bisoprolol when combined with Clidinium. Irritable bowel syndrome [DD91] [18]
Dicyclomine DMZSDGX Moderate Antagonize the effect of Bisoprolol when combined with Dicyclomine. Irritable bowel syndrome [DD91] [18]
Lanthanum carbonate DMMJQSH Moderate Decreased absorption of Bisoprolol due to formation of complexes caused by Lanthanum carbonate. Mineral absorption/transport disorder [5C64] [23]
Thalidomide DM70BU5 Moderate Increased risk of ventricular arrhythmias by the combination of Bisoprolol and Thalidomide. Multiple myeloma [2A83] [26]
Siponimod DM2R86O Major Increased risk of bradycardia by the combination of Bisoprolol and Siponimod. Multiple sclerosis [8A40] [26]
Fingolimod DM5JVAN Major Increased risk of bradycardia by the combination of Bisoprolol and Fingolimod. Multiple sclerosis [8A40] [27]
Ozanimod DMT6AM2 Moderate Increased risk of atrioventricular block by the combination of Bisoprolol and Ozanimod. Multiple sclerosis [8A40] [28]
Promethazine DM6I5GR Moderate Additive hypotensive effects by the combination of Bisoprolol and Promethazine. Nausea/vomiting [MD90] [21]
Methylscopolamine DM5VWOB Moderate Antagonize the effect of Bisoprolol when combined with Methylscopolamine. Peptic ulcer [DA61] [18]
Terazosin DM3JCVS Moderate Additive hypotensive effects by the combination of Bisoprolol and Terazosin. Prostate hyperplasia [GA90] [24]
Levomepromazine DMIKFEL Moderate Additive hypotensive effects by the combination of Bisoprolol and Levomepromazine. Psychotic disorder [6A20-6A25] [21]
Fluphenazine DMIT8LX Moderate Additive hypotensive effects by the combination of Bisoprolol and Fluphenazine. Psychotic disorder [6A20-6A25] [21]
Quetiapine DM1N62C Moderate Additive hypotensive effects by the combination of Bisoprolol and Quetiapine. Schizophrenia [6A20] [21]
Mesoridazine DM2ZGAN Moderate Additive hypotensive effects by the combination of Bisoprolol and Mesoridazine. Schizophrenia [6A20] [21]
Thioridazine DM35M8J Moderate Additive hypotensive effects by the combination of Bisoprolol and Thioridazine. Schizophrenia [6A20] [21]
Aripiprazole DM3NUMH Moderate Additive hypotensive effects by the combination of Bisoprolol and Aripiprazole. Schizophrenia [6A20] [21]
Iloperidone DM6AUFY Moderate Additive hypotensive effects by the combination of Bisoprolol and Iloperidone. Schizophrenia [6A20] [21]
Paliperidone DM7NPJS Moderate Additive hypotensive effects by the combination of Bisoprolol and Paliperidone. Schizophrenia [6A20] [21]
Perphenazine DMA4MRX Moderate Additive hypotensive effects by the combination of Bisoprolol and Perphenazine. Schizophrenia [6A20] [21]
Molindone DMAH70G Moderate Additive hypotensive effects by the combination of Bisoprolol and Molindone. Schizophrenia [6A20] [21]
Thiothixene DMDINC4 Moderate Additive hypotensive effects by the combination of Bisoprolol and Thiothixene. Schizophrenia [6A20] [21]
Risperidone DMN6DXL Moderate Additive hypotensive effects by the combination of Bisoprolol and Risperidone. Schizophrenia [6A20] [21]
Amisulpride DMSJVAM Moderate Increased risk of ventricular arrhythmias by the combination of Bisoprolol and Amisulpride. Schizophrenia [6A20] [18]
Asenapine DMSQZE2 Moderate Additive hypotensive effects by the combination of Bisoprolol and Asenapine. Schizophrenia [6A20] [21]
Pipecuronium DM5F84A Moderate Additive neuromuscular blocking effects by the combination of Bisoprolol and Pipecuronium. Tonus and reflex abnormality [MB47] [22]
Doxacurium DMKE7L9 Moderate Additive neuromuscular blocking effects by the combination of Bisoprolol and Doxacurium. Tonus and reflex abnormality [MB47] [22]
Vecuronium DMP0UK2 Moderate Additive neuromuscular blocking effects by the combination of Bisoprolol and Vecuronium. Tonus and reflex abnormality [MB47] [22]
Rocuronium DMY9BMK Moderate Additive neuromuscular blocking effects by the combination of Bisoprolol and Rocuronium. Tonus and reflex abnormality [MB47] [22]
Methdilazine DMAUHQX Moderate Additive hypotensive effects by the combination of Bisoprolol and Methdilazine. Vasomotor/allergic rhinitis [CA08] [21]
Trimeprazine DMEMV9D Moderate Additive hypotensive effects by the combination of Bisoprolol and Trimeprazine. Vasomotor/allergic rhinitis [CA08] [29]
Amiodarone DMUTEX3 Moderate Increased risk of atrioventricular block by the combination of Bisoprolol and Amiodarone. Ventricular tachyarrhythmia [BC71] [30]
⏷ Show the Full List of 57 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Allura red AC dye E00338 33258 Colorant
FD&C blue no. 2 E00446 2723854 Colorant
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sunset yellow FCF E00255 17730 Colorant
Beta-D-lactose E00099 6134 Diluent; Dry powder inhaler carrier; Lyophilization aid
Calcium hydrogenphosphate E00294 24441 Diluent
Carmellose sodium E00625 Not Available Disintegrant
Crospovidone E00626 Not Available Disintegrant
Eisenoxyd E00585 56841934 Colorant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Hypromellose E00634 Not Available Coating agent
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 400 E00653 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 4000 E00654 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 6000 E00655 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80 E00665 Not Available Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Triacetin E00080 5541 Humectant; Plasticizing agent; Solvent
Certolake sunset yellow E00351 61817 Colorant
Haematite red E00236 14833 Colorant
Hydrophobic colloidal silica E00285 24261 Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
Pregelatinized starch E00674 Not Available Binding agent; Diluent; Disintegrant
⏷ Show the Full List of 25 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Bisoprolol 5 mg tablet 5 mg Oral Tablet Oral
Bisoprolol 10 mg tablet 10 mg Oral Tablet Oral
Bisoprolol Fumarate 5mg tablet 5mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7129).
2 Bisoprolol FDA Label
3 BDDCS applied to over 900 drugs
4 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.
5 Bisoprolol monograph
6 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.
7 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
8 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
9 Summary of product characteristics
10 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
11 Antiarrhythmic effect of bisoprolol, a highly selective beta1-blocker, in patients with paroxysmal atrial fibrillation. Int Heart J. 2008 May;49(3):281-93.
12 Stereoselective metabolism of bisoprolol enantiomers in dogs and humans. Life Sci. 1998;63(13):1097-108.
13 Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22.
14 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.
15 The effects of 1 month antihypertensive treatment with perindopril, bisoprolol or both on the ex vivo ability of monocytes to secrete inflammatory cytokines. Int J Clin Pharmacol Ther. 2009 Nov;47(11):686-94. doi: 10.5414/cpp47686.
16 Anastassiades CJ "Nifedipine and beta-blocker drugs." Br Med J 281 (1980): 1251-2. [PMID: 6107167]
17 Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA "Nadolol in combination with indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol 28 (1985): 29-33. [PMID: 3987783]
18 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
19 Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
20 Product Information. Zylo Filmtab (zileuton). Abbott Pharmaceutical, Abbott Park, IL.
21 Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
22 Chapple DJ, Clark JS, Hughes R "Interaction between atracurium and drugs used in anaesthesia." Br J Anaesth 55 Suppl 1 (1983): s17-22. [PMID: 6688011]
23 Canadian Pharmacists Association.
24 Chrysant SG "Experience with terazosin administered in combination with other antihypertensive agents." Am J Med 80 (1986): 55-61. [PMID: 2872808]
25 Kirch W, Rose I, Klingmann I, Pabst J, Ohnhaus EE "Interaction of bisoprolol with cimetidine and rifampicin." Eur J Clin Pharmacol 31 (1986): 59-62. [PMID: 2877885]
26 Cerner Multum, Inc. "Australian Product Information.".
27 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
28 Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
29 Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
30 Leor J, Levartowsky D, Sharon C, Farfel Z "Amiodarone and beta-adrenergic blockers: an interaction with metoprolol but not with atenolol." Am Heart J 16 (1988): 206-7. [PMID: 3394625]