Details
Stereochemistry | ACHIRAL |
Molecular Formula | C31H33N3O6S |
Molecular Weight | 575.675 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC(=CC=C1CC2=CN(C)C3=C2C=C(NC(=O)OC4CCCC4)C=C3)C(=O)NS(=O)(=O)C5=CC=CC=C5C
InChI
InChIKey=YEEZWCHGZNKEEK-UHFFFAOYSA-N
InChI=1S/C31H33N3O6S/c1-20-8-4-7-11-29(20)41(37,38)33-30(35)22-13-12-21(28(17-22)39-3)16-23-19-34(2)27-15-14-24(18-26(23)27)32-31(36)40-25-9-5-6-10-25/h4,7-8,11-15,17-19,25H,5-6,9-10,16H2,1-3H3,(H,32,36)(H,33,35)
DescriptionCurator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020547s027lbl.pdf
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020547s027lbl.pdf
Zafirlukast is an oral leukotriene receptor antagonist (LTRA) for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. Zafirlukast is indicated for the prophylaxis and chronic treatment of asthma. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD4 than nonasthmatic subjects. In vitro studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC4, LTD4 and LTE4) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD4-induced increases in cutaneous vascular permeability and inhibited inhaled LTD4-induced influx of eosinophils into animal lungs. Zafirlukast is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma. Zafirlukast is marketed by Astra Zeneca with the brand names Accolate, Accoleit, and Vanticon. It was the first LTRA to be marketed in the USA and is now approved in over 60 countries, including the UK, Japan, Taiwan, Italy, Spain, Canada, Brazil, China and Turkey.
CNS Activity
Sources: https://www.drugs.com/pro/zafirlukast.html
Curator's Comment: Studies in rats using radiolabeled Zafirlukast indicate minimal distribution across the blood-brain barrier.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
1.1 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ACCOLATE Approved UseACCOLATE is indicated for the prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older. Launch Date1996 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
352.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11888331 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
ZAFIRLUKAST plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1090.41 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11888331 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
ZAFIRLUKAST plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.3 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11888331 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
ZAFIRLUKAST plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Other AEs: Pharyngitis, Headache... Other AEs: Pharyngitis (24.7%) Sources: Headache (13.8%) Myalgia (3.7%) Sinusitis (3.5%) Flu syndrome (3.3%) Cough increased (3.1%) Rash (3.1%) Rhinitis (3.1%) Accidental injury (3.1%) Nausea (3.1%) Back pain (2.9%) Hypertonia (2.9%) Diarrhea (2.7%) Exacerbation of asthma (2.7%) |
20 mg 2 times / day multiple, oral Highest studied dose Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 37 |
Other AEs: Headache, Gastritis... Other AEs: Headache (7%) Sources: Gastritis (1%) Pharyngitis (20%) Rhinitis (7%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Headache | 13.8% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Diarrhea | 2.7% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Exacerbation of asthma | 2.7% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Back pain | 2.9% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Hypertonia | 2.9% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Pharyngitis | 24.7% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Accidental injury | 3.1% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Cough increased | 3.1% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Nausea | 3.1% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Rash | 3.1% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Rhinitis | 3.1% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Flu syndrome | 3.3% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Sinusitis | 3.5% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Myalgia | 3.7% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 12-76 |
Gastritis | 1% | 20 mg 2 times / day multiple, oral Highest studied dose Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 37 |
Pharyngitis | 20% | 20 mg 2 times / day multiple, oral Highest studied dose Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 37 |
Headache | 7% | 20 mg 2 times / day multiple, oral Highest studied dose Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 37 |
Rhinitis | 7% | 20 mg 2 times / day multiple, oral Highest studied dose Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, 37 |
PubMed
Title | Date | PubMed |
---|---|---|
[Zafirlukast inhibition of leukotriene C4 induced endothelin-1 expression in human airway structural cell]. | 2000 Oct |
|
Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma. | 2001 |
|
Pharmacology of airway afferent nerve activity. | 2001 |
|
The role of leukotriene receptor antagonists in the treatment of chronic asthma in childhood. | 2001 |
|
Pathophysiology of the cysteinyl leukotrienes and effects of leukotriene receptor antagonists in asthma. | 2001 |
|
Enhanced prostaglandin E2 secretion in sputum from asthmatic patients after zafirlukast therapy. | 2001 Apr |
|
Modulation of the immediate allergic wheal reaction in the skin by drugs inhibiting the effects of leukotriene C4 and prostaglandin D2. | 2001 Apr |
|
A comparison of short-term treatment with inhaled fluticasone propionate and zafirlukast for patients with persistent asthma. | 2001 Aug 15 |
|
Allergy and angiitis: two aspects of Churg-Strauss syndrome. | 2001 Feb |
|
The role of antileukotrienes in the treatment of asthma. | 2001 Jun |
|
Role of cysteinyl leukotrienes in nociceptive and inflammatory conditions in experimental animals. | 2001 Jun 29 |
|
Use of changes in symptoms to predict changes in lung function in assessing the response to asthma therapy. | 2001 May |
|
Molecular cloning and functional characterization of murine cysteinyl-leukotriene 1 (CysLT(1)) receptors. | 2001 Nov 1 |
|
The effect of low-dose inhaled fluticasone propionate on exhaled nitric oxide in asthmatic patients and comparison with oral zafirlukast. | 2001 Oct |
|
Asthma treatment with inhaled corticosteroids versus antileukotrienes: what exhaled nitric oxide studies do and do not tell us. | 2001 Oct |
|
Severe liver injury. | 2001 Oct 2 |
|
Fulminant eosinophilic endomyocarditis in an asthmatic patient treated with pranlukast after corticosteroid withdrawal. | 2001 Sep |
|
Leukotriene receptor antagonists in the treatment of asthma: an update. | 2002 |
|
Pharmacokinetic profile of zafirlukast. | 2002 |
|
Pharmacogenetics of asthma. | 2002 Apr 1 |
|
Vasculitis induced by zafirlukast therapy. | 2002 Aug |
|
Chemoprevention by lipoxygenase and leukotriene pathway inhibitors of vinyl carbamate-induced lung tumors in mice. | 2002 Aug 1 |
|
Participation of chemical mediators other than histamine in nasal allergy signs: a study using mice lacking histamine H(1) receptors. | 2002 Aug 9 |
|
Economic impact of asthma therapy with fluticasone propionate, montelukast, or zafirlukast in a managed care population. | 2002 Feb |
|
[Churg-Strauss syndrome after treatment with Singulair (montelukast)]. | 2002 Feb 20 |
|
[Study on relationship between leukotrienes and exercise-induced asthma]. | 2002 Jan 10 |
|
Effects of adding either a leukotriene receptor antagonist or low-dose theophylline to a low or medium dose of inhaled corticosteroid in patients with persistent asthma. | 2002 Jul |
|
Efficacy and safety of low-dose fluticasone propionate compared with zafirlukast in patients with persistent asthma. | 2002 Jul |
|
Churg-Strauss syndrome in a case of asthma. | 2002 Jul |
|
5-Lipoxygenase polymorphism and in-vivo response to leukotriene receptor antagonists. | 2002 Jun |
|
Prevalence of serious eosinophilia and incidence of Churg-Strauss syndrome in a cohort of asthma patients. | 2002 Mar |
|
Treatment of canine atopic dermatitis with zafirlukast, a leukotriene-receptor antagonist: a single-blinded, placebo-controlled study. | 2002 Mar |
|
Inhaled fluticasone and zafirlukast in persistent asthma. | 2002 Mar |
|
[Aspirin induced asthma, urinary leukotriene E4 and zafirlukast]. | 2002 Mar-Apr |
|
Comparison of second controller medications in addition to inhaled corticosteroid in patients with moderate asthma. | 2002 May |
Sample Use Guides
Should be taken at least 1 hour before or 2 hours after meals. Adults and Children 12 years of age and older
The recommended dose of ACCOLATE in adults and children 12 years and older is 20 mg twice daily. Pediatric Patients 5 through 11 years of age
The recommended dose of ACCOLATE in children 5 through 11 years of age is 10 mg twice daily.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9647482
Zafirlukast significantly inhibited 10 uM LTD4-evoked 35SO4 output in a concentration-dependent fashion, with maximal inhibition of 78% at 10 uM zafirlukast, and IC50 value of 0.6 uM.
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C29712
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Zafirlukast
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ZAFIRLUKAST
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PRIMARY | Cytochrome P450 2C9 Inhibitors [MoA] |
ACTIVE MOIETY