Details of the Drug

General Information of Drug (ID: DMFDC0Q)

• Drug Name: Tiotropium
• Synonyms: 186691-13-4; UNII-0EB439235F; 0EB439235F; [3H]tiotropium; (1r,2r,4s,5s,7s)-7-{[hydroxy(Dithiophen-2-Yl)acetyl]oxy}-9,9-Dimethyl-3-Oxa-9-Azoniatricyclo[3310~2,4~]nonane; NCGC00167971-01; 0HK; (1R,2R,4S,5S)-7-{[2-hydroxy-2,2-bis(thiophen-2-yl)acetyl]oxy}-9,9-dimethyl-3-oxa-9-azatricyclo[3310^{2,4}]nonan-9-ium; GTPL367; SCHEMBL4662461; GTPL8592; DTXSID5044281; CHEMBL3305968; Spiriva (TN); Tiotropium bromide [USAN:INN]; (1A,2A,4A,5A,7A)-7-[(Hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatri-cyclo[331024]nonane bromide; (1a,2,4,5a,7)-7-[(2-Hydroxy-2,2-di-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[33102,4]nonane bromide; 7-{[hydroxy(dithiophen-2-yl)acetyl]oxy}-9,9-dimethyl-3-oxa-9-azoniatricyclo[33102,4]nonane bromide

Indication

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Approved	[1]
Pulmonary emphysema	CA21.Z	Approved	[2]
Asthma	CA23	Investigative	[2]

• Therapeutic Class: Bronchodilator Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 392.5
  Logarithm of the Partition Coefficient (xlogp); 2.3
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 1.65 mg/L [3]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 12 min [3]
  Bioavailability: The bioavailability of drug is 50-81% [3]
  Clearance: The renal clearance of drug is 669 mL/min [4]
  Elimination: 74% of intravenous tiotropium was excreted unchanged in urine.[A180163,L7084,L7087,L7090,L7093] 14% of a dry powder inhalation dose was excreted unchanged in the urine [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 24 hours [5]
  Vd: The volume of distribution (Vd) of drug is 32 L/kg [4]
• Chemical Identifiers:
  Formula: C19H22NO4S2+
  IUPAC Name: [(1S,2S,4R,5R)-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonan-7-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate
  Canonical SMILES: C[N+]1([C@@H]2CC(C[C@H]1[C@H]3[C@@H]2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C
  InChI: InChI=1S/C19H22NO4S2/c1-20(2)12-9-11(10-13(20)17-16(12)24-17)23-18(21)19(22,14-5-3-7-25-14)15-6-4-8-26-15/h3-8,11-13,16-17,22H,9-10H2,1-2H3/q+1/t11?,12-,13+,16-,17+
  InChIKey: LERNTVKEWCAPOY-FPISHFTHSA-N
• Cross-matching ID:
  PubChem CID: 5487427
  ChEBI ID: CHEBI:90960
  CAS Number: 186691-13-4
  DrugBank ID: DB01409
  TTD ID: D0P1WA
  VARIDT ID: DR00017
  ACDINA ID: D00681
• 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
Muscarinic acetylcholine receptor (CHRM)	TTOXS3C	NOUNIPROTAC	Antagonist	[6]
Muscarinic acetylcholine receptor M3 (CHRM3)	TTQ13Z5	ACM3_HUMAN	Antagonist	[7]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation/carnitine transporter 2 (SLC22A5)	DT3HUVD	S22A5_HUMAN	Substrate	[8]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[9]

Molecular Expression Atlas of This Drug

• The Studied Disease: Chronic obstructive pulmonary disease
• ICD Disease Classification: CA22

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Muscarinic acetylcholine receptor M3 (CHRM3)	DTT	CHRM3	4.61E-07	-0.59	-0.73
Organic cation transporter 1 (SLC22A1)	DTP	SLC22A1	8.54E-01	1.24E-02	7.20E-02
Organic cation/carnitine transporter 2 (SLC22A5)	DTP	OCTN2	3.49E-09	1.50E-01	6.50E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Tiotropium

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Umeclidinium	DM4E8O9	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Umeclidinium.	Chronic obstructive pulmonary disease [CA22]	[10]
Revefenacin	DMMP5SI	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Revefenacin.	Chronic obstructive pulmonary disease [CA22]	[10]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Mepyramine	DMB4SFH	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Mepyramine.	Allergic/hypersensitivity disorder [4A80-4A8Z]	[11]
Phenyltoloxamine	DMKAEQW	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Phenyltoloxamine.	Allergic/hypersensitivity disorder [4A80-4A8Z]	[11]
Acetylcholine	DMDF79Z	Moderate	Antagonize the effect of Tiotropium when combined with Acetylcholine.	Cataract [9B10]	[12]
Mepenzolate	DM8YU2F	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Mepenzolate.	Digestive system disease [DE2Z]	[10]
Solifenacin	DMG592Q	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Solifenacin.	Functional bladder disorder [GC50]	[10]
Belladonna	DM2RBWK	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Belladonna.	Infectious gastroenteritis/colitis [1A40]	[10]
R0-93877	DMM4U9G	Moderate	Antagonize the effect of Tiotropium when combined with R0-93877.	Irritable bowel syndrome [DD91]	[13]
Phenindamine	DMDTC7R	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Phenindamine.	Nasopharyngitis [CA00]	[10]
Methylscopolamine	DM5VWOB	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Methylscopolamine.	Peptic ulcer [DA61]	[10]
Molindone	DMAH70G	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Molindone.	Schizophrenia [6A20]	[10]
Thiothixene	DMDINC4	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Thiothixene.	Schizophrenia [6A20]	[10]
Acrivastine	DMTIGA0	Moderate	Additive anticholinergic effects by the combination of Tiotropium and Acrivastine.	Vasomotor/allergic rhinitis [CA08]	[10]

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Tiotropium 0.018 mg powder	0.018 mg	Inhalant Powder	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: 367).
• [2] Tiotropium FDA Label
• [3] Encyclopedia
• [4] Price D, Sharma A, Cerasoli F: Biochemical properties, pharmacokinetics and pharmacological response of tiotropium in chronic obstructive pulmonary disease patients. Expert Opin Drug Metab Toxicol. 2009 Apr;5(4):417-24. doi: 10.1517/17425250902828337 .
• [5] FDA Approved Drug Products: Tiotropium Inhalation Spray
• [6] Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70.
• [7] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [8] Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol Pharm. 2010 Feb 1;7(1):187-95.
• [9] Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
• [10] Cole JM, Sheehan AH, Jordan JK "Concomitant use of ipratropium and tiotropium in chronic obstructive plmonary disease." Ann Pharmacother 46 (2012): 1717-21. [PMID: 23170031]
• [11] Product Information. Anoro Ellipta (umeclidinium-vilanterol). GlaxoSmithKline, Research Triangle Park, NC.
• [12] Multum Information Services, Inc. Expert Review Panel.
• [13] EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports.".