General Information of Drug (ID: DMYM974)

Drug Name
Arformoterol
Synonyms 67346-49-0; Brovana; UNII-F91H02EBWT; Arformoterol tartrate; CHEMBL1363; F91H02EBWT; CHEBI:408174; Brovana (TN); Formoterol/fluticasone propionate
Indication
Disease Entry ICD 11 Status REF
Chronic obstructive pulmonary disease CA22 Approved [1]
Pulmonary emphysema CA21.Z Approved [2]
Asthma CA23 Phase 4 [3]
Therapeutic Class
Bronchodilator Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 344.4
Logarithm of the Partition Coefficient (xlogp) 1.8
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
Clearance
The renal clearance of drug is 8.9 L/h []
Elimination
8% of drug is excreted from urine in the unchanged form [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 26 hours [5]
Metabolism
The drug is metabolized via the cytochrome P450 enzym []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.001 micromolar/kg/day [6]
Water Solubility
The ability of drug to dissolve in water is measured as 0.66 mg/mL [4]
Chemical Identifiers
Formula
C19H24N2O4
IUPAC Name
N-[2-hydroxy-5-[(1R)-1-hydroxy-2-[[(2R)-1-(4-methoxyphenyl)propan-2-yl]amino]ethyl]phenyl]formamide
Canonical SMILES
C[C@H](CC1=CC=C(C=C1)OC)NC[C@@H](C2=CC(=C(C=C2)O)NC=O)O
InChI
InChI=1S/C19H24N2O4/c1-13(9-14-3-6-16(25-2)7-4-14)20-11-19(24)15-5-8-18(23)17(10-15)21-12-22/h3-8,10,12-13,19-20,23-24H,9,11H2,1-2H3,(H,21,22)/t13-,19+/m1/s1
InChIKey
BPZSYCZIITTYBL-YJYMSZOUSA-N
Cross-matching ID
PubChem CID
3083544
ChEBI ID
CHEBI:408174
CAS Number
67346-49-0
DrugBank ID
DB01274
TTD ID
D0D1DI
INTEDE ID
DR0131
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-2 (ADRB2) TT2CJVK ADRB2_HUMAN Agonist [7]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2D6 (CYP2D6)
Main DME
DECB0K3 CP2D6_HUMAN Substrate [8]
Mephenytoin 4-hydroxylase (CYP2C19)
Main DME
DEGTFWK CP2CJ_HUMAN Substrate [8]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Substrate [8]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Gene/Protein Processing [9]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [10]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Gene/Protein Processing [11]
Eosinophil cationic protein (RNASE3) OTVE2XD1 ECP_HUMAN Gene/Protein Processing [12]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Gene/Protein Processing [13]
Solute carrier family 22 member 3 (SLC22A3) OTQYGVXX S22A3_HUMAN Regulation of Drug Effects [14]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

ICD Disease Classification 12 Disease of the respiratory system
Disease Class ICD-11: CA23 Asthma
The Studied Tissue Lung tissue
The Studied Disease Chronic obstructive pulmonary disease [ICD-11:CA23]
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Adrenergic receptor beta-2 (ADRB2) DTT ADRB2 4.88E-01 -0.05 -0.12
Adrenergic receptor beta-2 (ADRB2) DTT ADRB2 7.10E-01 0.06 0.09
Cytochrome P450 2A6 (CYP2A6) DME CYP2A6 4.70E-01 2.63E-01 6.12E-01
Cytochrome P450 2A6 (CYP2A6) DME CYP2A6 1.35E-03 -2.46E-01 -5.85E-01
Mephenytoin 4-hydroxylase (CYP2C19) DME CYP2C19 4.79E-03 1.32E-01 7.85E-01
Mephenytoin 4-hydroxylase (CYP2C19) DME CYP2C19 1.82E-01 -1.71E-02 -9.86E-02
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 8.01E-02 6.73E-02 3.36E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 2.91E-04 1.41E-01 6.14E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Arformoterol (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Methylene blue DMJAPE7 Moderate Additive hypertensive effects by the combination of Arformoterol and Methylene blue. Acquired methaemoglobinaemia [3A93] [15]
Ivosidenib DM8S6T7 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Ivosidenib. Acute myeloid leukaemia [2A60] [16]
Midostaurin DMI6E0R Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Midostaurin. Acute myeloid leukaemia [2A60] [16]
Arn-509 DMT81LZ Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Arn-509. Acute myeloid leukaemia [2A60] [16]
Gilteritinib DMTI0ZO Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Gilteritinib. Acute myeloid leukaemia [2A60] [16]
Oliceridine DM6MDCF Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Oliceridine. Acute pain [MG31] [16]
Ivabradine DM0L594 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Ivabradine. Angina pectoris [BA40] [16]
Dronedarone DMA8FS5 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Dronedarone. Angina pectoris [BA40] [16]
Bedaquiline DM3906J Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [16]
Droxidopa DM5YF4M Moderate Additive hypertensive effects by the combination of Arformoterol and Droxidopa. Autonomic nervous system disorder [8D87] [17]
Retigabine DMGNYIH Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Retigabine. Behcet disease [4A62] [16]
Eribulin DM1DX4Q Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Eribulin. Breast cancer [2C60-2C6Y] [16]
Bosutinib DMTI8YE Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Bosutinib. Breast cancer [2C60-2C6Y] [16]
Corticotropin DMP9TWZ Minor Increased risk of hypokalemia by the combination of Arformoterol and Corticotropin. Chronic kidney disease [GB61] [18]
PF-04449913 DMSB068 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and PF-04449913. Chronic myelomonocytic leukaemia [2A40] [16]
Levomilnacipran DMV26S8 Moderate Increased risk of rapid heart rate by the combination of Arformoterol and Levomilnacipran. Chronic pain [MG30] [19]
Probucol DMVZQ2M Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Probucol. Coronary atherosclerosis [BA80] [16]
Pasireotide DMHM7JS Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Pasireotide. Cushing syndrome [5A70] [16]
Osilodrostat DMIJC9X Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Osilodrostat. Cushing syndrome [5A70] [16]
Milnacipran DMBFE74 Moderate Increased risk of rapid heart rate by the combination of Arformoterol and Milnacipran. Depression [6A70-6A7Z] [19]
Desvenlafaxine DMHD4PE Moderate Additive hypertensive effects by the combination of Arformoterol and Desvenlafaxine. Depression [6A70-6A7Z] [19]
Tetrabenazine DMYWQ0O Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Tetrabenazine. Dissociative neurological symptom disorder [6B60] [16]
Deutetrabenazine DMUPFLI Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Deutetrabenazine. Dystonic disorder [8A02] [16]
Ingrezza DMVPLNC Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Ingrezza. Dystonic disorder [8A02] [16]
Solifenacin DMG592Q Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Solifenacin. Functional bladder disorder [GC50] [16]
Fostemsavir DM50ILT Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Fostemsavir. Human immunodeficiency virus disease [1C60-1C62] [16]
Lopinavir DMITQS0 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Lopinavir. Human immunodeficiency virus disease [1C60-1C62] [20]
Rilpivirine DMJ0QOW Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Rilpivirine. Human immunodeficiency virus disease [1C60-1C62] [16]
Crizotinib DM4F29C Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Crizotinib. Lung cancer [2C25] [16]
Ceritinib DMB920Z Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Ceritinib. Lung cancer [2C25] [16]
Osimertinib DMRJLAT Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Osimertinib. Lung cancer [2C25] [16]
Selpercatinib DMZR15V Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Selpercatinib. Lung cancer [2C25] [16]
Lumefantrine DM29GAD Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Lumefantrine. Malaria [1F40-1F45] [20]
Inotuzumab ozogamicin DMAC130 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Inotuzumab ozogamicin. Malignant haematopoietic neoplasm [2B33] [16]
Vemurafenib DM62UG5 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Vemurafenib. Melanoma [2C30] [16]
LGX818 DMNQXV8 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and LGX818. Melanoma [2C30] [16]
Panobinostat DM58WKG Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Panobinostat. Multiple myeloma [2A83] [16]
Siponimod DM2R86O Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Siponimod. Multiple sclerosis [8A40] [16]
Fingolimod DM5JVAN Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Fingolimod. Multiple sclerosis [8A40] [16]
Ozanimod DMT6AM2 Major Increased risk of ventricular arrhythmias by the combination of Arformoterol and Ozanimod. Multiple sclerosis [8A40] [21]
Romidepsin DMT5GNL Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Romidepsin. Mycosis fungoides [2B01] [16]
Nilotinib DM7HXWT Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Nilotinib. Myeloproliferative neoplasm [2A20] [16]
Entrectinib DMMPTLH Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Entrectinib. Non-small cell lung cancer [2C25] [16]
Rucaparib DM9PVX8 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Rucaparib. Ovarian cancer [2C73] [16]
Triclabendazole DMPWGBR Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Triclabendazole. Parasitic worm infestation [1F90] [16]
Safinamide DM0YWJC Moderate Additive hypertensive effects by the combination of Arformoterol and Safinamide. Parkinsonism [8A00] [15]
Rasagiline DM3WKQ4 Moderate Additive hypertensive effects by the combination of Arformoterol and Rasagiline. Parkinsonism [8A00] [15]
Pimavanserin DMR7IVC Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Pimavanserin. Parkinsonism [8A00] [16]
Macimorelin DMQYJIR Major Increased risk of prolong QT interval by the combination of Arformoterol and Macimorelin. Pituitary gland disorder [5A60-5A61] [22]
Lefamulin DME6G97 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Lefamulin. Pneumonia [CA40] [16]
Degarelix DM3O8QY Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Degarelix. Prostate cancer [2C82] [16]
ABIRATERONE DM8V75C Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and ABIRATERONE. Prostate cancer [2C82] [16]
Enzalutamide DMGL19D Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Enzalutamide. Prostate cancer [2C82] [16]
Levomepromazine DMIKFEL Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Levomepromazine. Psychotic disorder [6A20-6A25] [16]
Ciclesonide DM2NA4K Minor Increased risk of hypokalemia by the combination of Arformoterol and Ciclesonide. Respiratory system disease [CB40-CB7Z] [18]
Iloperidone DM6AUFY Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Iloperidone. Schizophrenia [6A20] [16]
Amisulpride DMSJVAM Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Amisulpride. Schizophrenia [6A20] [16]
Asenapine DMSQZE2 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Asenapine. Schizophrenia [6A20] [16]
LEE011 DMMX75K Major Increased risk of prolong QT interval by the combination of Arformoterol and LEE011. Solid tumour/cancer [2A00-2F9Z] [23]
Vandetanib DMRICNP Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Vandetanib. Solid tumour/cancer [2A00-2F9Z] [16]
Triptorelin DMTK4LS Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Triptorelin. Solid tumour/cancer [2A00-2F9Z] [16]
Pitolisant DM8RFNJ Moderate Increased risk of prolong QT interval by the combination of Arformoterol and Pitolisant. Somnolence [MG42] [16]
Telavancin DM58VQX Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Telavancin. Staphylococcal/streptococcal disease [1B5Y] [16]
Lenvatinib DMB1IU4 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Lenvatinib. Thyroid cancer [2D10] [16]
Cabozantinib DMIYDT4 Moderate Increased risk of ventricular arrhythmias by the combination of Arformoterol and Cabozantinib. Thyroid cancer [2D10] [16]
Fluticasone DMGCSVF Minor Increased risk of hypokalemia by the combination of Arformoterol and Fluticasone. Vasomotor/allergic rhinitis [CA08] [18]
⏷ Show the Full List of 66 DDI Information 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: 7479).
2 Arformoterol FDA Label
3 ClinicalTrials.gov (NCT02491970) Study to Evaluate Small Airway Parameters of Fluticasone/Formoterol (Flutiform) Compared to Fluticasone/Salmeterol in Asthma Patients.
4 BDDCS applied to over 900 drugs
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 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
7 Arformoterol tartrate in the treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease. Drugs Today (Barc). 2009 Jan;45(1):3-9.
8 A comparison of the expression and metabolizing activities of phase I and II enzymes in freshly isolated human lung parenchymal cells and cryopreserved human hepatocytes. Drug Metab Dispos. 2007 Oct;35(10):1797-805.
9 The 2-subtype of adrenoceptors mediates inhibition of pro-fibrotic events in human lung fibroblasts. Naunyn Schmiedebergs Arch Pharmacol. 2011 Aug;384(2):133-45. doi: 10.1007/s00210-011-0655-5. Epub 2011 May 21.
10 Long-acting beta2-adrenergic formoterol and salmeterol induce the apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 2004 Jan;124(2):141-50. doi: 10.1046/j.1365-2141.2003.04746.x.
11 Development of 3D-QSAR models for predicting the activities of chemicals to stimulate muscle growth via (2)-adrenoceptor. Toxicol In Vitro. 2021 Dec;77:105251. doi: 10.1016/j.tiv.2021.105251. Epub 2021 Sep 30.
12 Formoterol compared with beclomethasone and placebo on allergen-induced asthmatic responses. Am Rev Respir Dis. 1992 Nov;146(5 Pt 1):1156-60. doi: 10.1164/ajrccm/146.5_Pt_1.1156.
13 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
14 The effect of corticosteroids on the disposal of long-acting beta2-agonists by airway smooth muscle cells. J Allergy Clin Immunol. 2007 Nov;120(5):1103-9. doi: 10.1016/j.jaci.2007.08.034. Epub 2007 Oct 17.
15 Adverse effects and complications of treatment with beta-adrenergic agonist drugs. Committee on drugs, the American Academy of Allergy and Immunology. J Allergy Clin Immunol 75 (1985): 443-9. [PMID: 2858503]
16 Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32. [PMID: 7042176]
17 Product Information. Northera (droxidopa). Chelsea Therapeutics Inc, Charlotte, NC.
18 Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
19 Product Information. Cymbalta (duloxetine). Lilly, Eli and Company, Indianapolis, IN.
20 Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
21 Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
22 Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
23 Canadian Pharmacists Association.