Details of the Drug

General Information of Drug (ID: DM62B78)

• Drug Name: Olodaterol
• Synonyms: BI-1744

Indication

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 386.4
  Logarithm of the Partition Coefficient (xlogp); 1.8
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  Clearance: The renal clearance of drug is 173 mL/min []
  Half-life: The concentration or amount of drug in body reduced by one-half in 22 hours [2]
  Metabolism: The drug is metabolized via the direct glucuronidation and by O-demethylation at the methoxy moiety followed by conjugation []
  Unbound Fraction: The unbound fraction of drug in plasma is 0.4% [2]
  Vd: The volume of distribution (Vd) of drug is 1110 L []
• Chemical Identifiers:
  Formula: C21H26N2O5
  IUPAC Name: 6-hydroxy-8-[(1R)-1-hydroxy-2-[[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one
  Canonical SMILES: CC(C)(CC1=CC=C(C=C1)OC)NC[C@@H](C2=C3C(=CC(=C2)O)NC(=O)CO3)O
  InChI: InChI=1S/C21H26N2O5/c1-21(2,10-13-4-6-15(27-3)7-5-13)22-11-18(25)16-8-14(24)9-17-20(16)28-12-19(26)23-17/h4-9,18,22,24-25H,10-12H2,1-3H3,(H,23,26)/t18-/m0/s1
  InChIKey: COUYJEVMBVSIHV-SFHVURJKSA-N
• Cross-matching ID:
  PubChem CID: 11504295
  ChEBI ID: CHEBI:82700
  CAS Number: 868049-49-4
  DrugBank ID: DB09080
  TTD ID: D04UTT
  INTEDE ID: DR1191

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	Modulator	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9) Main DME	DE5IED8	CP2C9_HUMAN	Substrate	[4]

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 2C9 (CYP2C9)	DME	CYP2C9	7.33E-02	5.59E-02	2.99E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	5.65E-03	-7.28E-02	-1.24E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Olodaterol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Moderate	Additive hypertensive effects by the combination of Olodaterol and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[5]
Ivosidenib	DM8S6T7	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Ivosidenib.	Acute myeloid leukaemia [2A60]	[6]
Gilteritinib	DMTI0ZO	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Gilteritinib.	Acute myeloid leukaemia [2A60]	[6]
Oliceridine	DM6MDCF	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Oliceridine.	Acute pain [MG31]	[6]
Ivabradine	DM0L594	Moderate	Increased risk of prolong QT interval by the combination of Olodaterol and Ivabradine.	Angina pectoris [BA40]	[6]
PF-04449913	DMSB068	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[6]
Osilodrostat	DMIJC9X	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Osilodrostat.	Cushing syndrome [5A70]	[6]
Deutetrabenazine	DMUPFLI	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Deutetrabenazine.	Dystonic disorder [8A02]	[6]
Ingrezza	DMVPLNC	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Ingrezza.	Dystonic disorder [8A02]	[6]
Fostemsavir	DM50ILT	Moderate	Increased risk of prolong QT interval by the combination of Olodaterol and Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[6]
Osimertinib	DMRJLAT	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Osimertinib.	Lung cancer [2C25]	[6]
Selpercatinib	DMZR15V	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Selpercatinib.	Lung cancer [2C25]	[6]
LGX818	DMNQXV8	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and LGX818.	Melanoma [2C30]	[6]
Siponimod	DM2R86O	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Siponimod.	Multiple sclerosis [8A40]	[6]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Ozanimod.	Multiple sclerosis [8A40]	[7]
Entrectinib	DMMPTLH	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Entrectinib.	Non-small cell lung cancer [2C25]	[6]
Rucaparib	DM9PVX8	Moderate	Increased risk of prolong QT interval by the combination of Olodaterol and Rucaparib.	Ovarian cancer [2C73]	[6]
Triclabendazole	DMPWGBR	Moderate	Increased risk of prolong QT interval by the combination of Olodaterol and Triclabendazole.	Parasitic worm infestation [1F90]	[6]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Olodaterol and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[8]
Lefamulin	DME6G97	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Lefamulin.	Pneumonia [CA40]	[6]
Relugolix	DMK7IWL	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Relugolix.	Prostate cancer [2C82]	[6]
LEE011	DMMX75K	Major	Increased risk of prolong QT interval by the combination of Olodaterol and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[9]
Pitolisant	DM8RFNJ	Moderate	Increased risk of ventricular arrhythmias by the combination of Olodaterol and Pitolisant.	Somnolence [MG42]	[6]

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: 7543).
• [2] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [3] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [4] FDA Label of Olodaterol. The 2020 official website of the U.S. Food and Drug Administration.
• [5] 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]
• [6] Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32. [PMID: 7042176]
• [7] Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
• [8] Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
• [9] Canadian Pharmacists Association.