Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C19H22NO4S2 |
| Molecular Weight | 392.512 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 5 / 6 |
| E/Z Centers | 0 |
| Charge | 1 |
SHOW SMILES / InChI
SMILES
C[N+]1(C)[C@H]2C[C@@H](C[C@@H]1[C@H]3O[C@@H]23)OC(=O)C(O)(C4=CC=CS4)C5=CC=CS5
InChI
InChIKey=LERNTVKEWCAPOY-DZZGSBJMSA-N
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+
| Molecular Formula | C19H21NO4S2 |
| Molecular Weight | 391.504 |
| Charge | 0 |
| Count |
|
| Stereochemistry | EPIMERIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 5 / 6 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionSources: http://www.drugbank.ca/drugs/DB01409Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021395s040lbl.pdf
https://www.ncbi.nlm.nih.gov/pubmed/19461900
Sources: http://www.drugbank.ca/drugs/DB01409
Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021395s040lbl.pdf
https://www.ncbi.nlm.nih.gov/pubmed/19461900
Tiotropium is a long–acting, antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3–receptors at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies prevention of methacholine–induced bronchoconstriction effects were dose–dependent and lasted longer than 24 hours. The bronchodilation following inhalation of tiotropium is predominantly a site–specific effect. Tiotropium is a muscarinic receptor antagonist, often referred to as an antimuscarinic or anticholinergic agent. Although it does not display selectivity for specific muscarinic receptors, on topical application it acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation, thus producing a bronchodilatory effect. Tiotropium is used in the management of chronic obstructive pulmonary disease (COPD).Tiotropium bromide capsules for inhalation are co-promoted by Boehringer-Ingelheim and Pfizer under the trade name Spiriva. It is also manufactured and marketed by Cipla under trade name Tiova.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19461900
Curator's Comment: As tiotropium bromide is electrically charged, it is not absorbed by the gastrointestinal tract and does not pass the blood-brain barrier.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL245 Sources: http://www.drugbank.ca/drugs/DB01409 |
0.0316 nM [Ki] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | SPIRIVA Approved UseSPIRIVA HANDIHALER (tiotropium bromide inhalation powder) is indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. SPIRIVA HANDIHALER is indicated to reduce exacerbations in COPD patients. Launch Date2004 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
10.5 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24165906 |
5 μg 1 times / day steady-state, respiratory dose: 5 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered: |
TIOTROPIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
22.1 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24165906 |
5 μg 1 times / day steady-state, respiratory dose: 5 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered: |
TIOTROPIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
25 h |
5 μg single, respiratory dose: 5 μg route of administration: Respiratory experiment type: SINGLE co-administered: |
TIOTROPIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
28% |
5 μg single, respiratory dose: 5 μg route of administration: Respiratory experiment type: SINGLE co-administered: |
TIOTROPIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
90 ug single, respiratory Overdose Dose: 90 ug Route: respiratory Route: single Dose: 90 ug Sources: |
unhealthy, 74 |
Disc. AE: Tachycardia... AEs leading to discontinuation/dose reduction: Tachycardia Sources: |
282 ug single, respiratory Overdose Dose: 282 ug Route: respiratory Route: single Dose: 282 ug Sources: |
healthy Health Status: healthy Sources: |
|
2.5 ug 1 times / day multiple, respiratory Recommended Dose: 2.5 ug, 1 times / day Route: respiratory Route: multiple Dose: 2.5 ug, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Immediate hypersensitivity reaction, Angioedema... AEs leading to discontinuation/dose reduction: Immediate hypersensitivity reaction Sources: Angioedema Bronchospasm Anaphylaxis Bronchospasm paradoxical |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Tachycardia | Disc. AE | 90 ug single, respiratory Overdose Dose: 90 ug Route: respiratory Route: single Dose: 90 ug Sources: |
unhealthy, 74 |
| Anaphylaxis | Disc. AE | 2.5 ug 1 times / day multiple, respiratory Recommended Dose: 2.5 ug, 1 times / day Route: respiratory Route: multiple Dose: 2.5 ug, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Angioedema | Disc. AE | 2.5 ug 1 times / day multiple, respiratory Recommended Dose: 2.5 ug, 1 times / day Route: respiratory Route: multiple Dose: 2.5 ug, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Bronchospasm paradoxical | Disc. AE | 2.5 ug 1 times / day multiple, respiratory Recommended Dose: 2.5 ug, 1 times / day Route: respiratory Route: multiple Dose: 2.5 ug, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Bronchospasm | Disc. AE | 2.5 ug 1 times / day multiple, respiratory Recommended Dose: 2.5 ug, 1 times / day Route: respiratory Route: multiple Dose: 2.5 ug, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Immediate hypersensitivity reaction | Disc. AE | 2.5 ug 1 times / day multiple, respiratory Recommended Dose: 2.5 ug, 1 times / day Route: respiratory Route: multiple Dose: 2.5 ug, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| major | ||||
| minor | ||||
| no |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 6.0 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. | 2013-05 |
|
| Quantifying the association and dissociation rates of unlabelled antagonists at the muscarinic M3 receptor. | 2006-08 |
|
| Ba 679 BR, a novel long-acting anticholinergic bronchodilator. | 1993 |
Patents
Sample Use Guides
The recommended dose of SPIRIVA HANDIHALER (Tiotropium) is two inhalations of the powder contents of one SPIRIVA capsule, once-daily, with the HANDIHALER device. Do not take more than one dose in 24 hours.
For administration of SPIRIVA HANDIHALER, a SPIRIVA capsule is placed into the center chamber of the HANDIHALER device. The SPIRIVA capsule is pierced by pressing and releasing the green piercing button on the side of the HANDIHALER device. The tiotropium formulation is dispersed into the air stream when the patient inhales through the mouthpiece
Route of Administration:
Respiratory
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22003289
Tiotropium bromide at > 15 pg/mL inhibited IL-8 production from both BEAS-2B cells and LFs (human lung fibroblasts) after LPS stimulation.
| Substance Class |
Chemical
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0EB439235F
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R03AL06
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N0000175370
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N0000175574
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NCI_THESAURUS |
C29704
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WHO-ATC |
R03BB54
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DB01409
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C76004
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0EB439235F
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C079890
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186691-13-4
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SUB25691
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DTXSID5044281
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0EB439235F
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Tiotropium
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100000089907
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69120
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Tiotropium
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT | |||
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EXCRETED UNCHANGED |
after intravenous infusion in healthy young male subjects
URINE
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METABOLIC ENZYME -> SUBSTRATE | |||
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SALT/SOLVATE -> PARENT | |||
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BINDER->LIGAND |
BINDING
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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METABOLITE -> PARENT |
FECAL; PLASMA; URINE
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METABOLITE INACTIVE -> PARENT | |||
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METABOLITE -> PARENT |
PLASMA
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METABOLITE INACTIVE -> PARENT |
nonenzymatically cleave
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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ACTIVE MOIETY |
| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
|---|---|---|---|---|---|---|
| Volume of Distribution | PHARMACOKINETIC |
|
INTRAVENOUS INFUSION |
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| Biological Half-life | PHARMACOKINETIC |
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INHALED ADMINISTRATION |
|
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| Tmax | PHARMACOKINETIC |
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AT STEADY-STATE |
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