Zafirlukast

From Wikipedia, the free encyclopedia
Jump to: navigation, search
"accolate" redirects here. It is not to be confused with accolade.
Zafirlukast
Zafirlukast.svg
Zafirlukast 3D ball-and-stick.png
Systematic (IUPAC) name
cyclopentyl 3-{2-methoxy-4-[(o-tolylsulfonyl)carbamoyl]benzyl}-1-methyl-1H-indol-5-ylcarbamate
Clinical data
Trade names Accolate
AHFS/Drugs.com monograph
MedlinePlus a697007
Pregnancy cat. B1 (Australia), B (United States)
Legal status POM (UK)
Routes Oral
Pharmacokinetic data
Bioavailability Unknown
Protein binding 99%
Metabolism Hepatic (CYP2C9-mediated)
Half-life 10 hours
Excretion Biliary
Identifiers
CAS number 107753-78-6 YesY
ATC code R03DC01
PubChem CID 5717
IUPHAR ligand 3322
DrugBank DB00549
ChemSpider 5515 YesY
UNII XZ629S5L50 YesY
KEGG D00411 YesY
ChEBI CHEBI:10100 YesY
ChEMBL CHEMBL603 YesY
Chemical data
Formula C31H33N3O6S 
Mol. mass 575.676 g/mol
 YesY (what is this?)  (verify)

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. Another leukotriene receptor antagonist is montelukast (Singulair), taken once daily. Zileuton (Zyflo), also used in the treatment of asthma via its inhibition of 5-lipoxygenase, is taken four times per day.

Zafirlukast blocks the action of the cysteinyl leukotrienes on the CysLT1 receptors, thus reducing constriction of the airways, build-up of mucus in the lungs and inflammation of the breathing passages.

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.

Pharmacokinetics[edit]

Healthy young men who received a single oral 40 mg dose attained peak plasma zafirlukast concentrations that averaged 607 μg/L at 3.4 hours. The elimination half-life ranged from 12 to 20 hours. In another study involving a 20 mg single oral dose in healthy men, the elimination half-life averaged 5.6 hours.[1][2]

Special warnings[edit]

A letter was submitted to the FDA by Zeneca Pharmaceuticals on July 22, 1997, notifying them of a change in product labeling that includes the following potential reaction in patients undergoing a dosage reduction of oral steroids who are currently taking zafirlukast:

PRECAUTIONS-Eosinophilic Conditions: The reduction of the oral steroid dose, in some patients on ACCOLATE therapy, has been followed in rare cases by the occurrence of eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy sometimes presenting as Churg–Strauss syndrome, a systemic eosinophilic vasculitis. Although a causal relationship with ACCOLATE has not been established, caution is required when oral steroid reduction is being considered.1

References[edit]

  1. ^ Fischer JD, Song MH, Suttle AB, Heizer WD, Burns CB, Vargo DL, Brouwer KL. Comparison of zafirlukast (Accolate) absorption after oral and colonic administration in humans. Pharmaceut. Res. 17: 154-159, 2000.
  2. ^ Bharathi DV, Naidu A, Jagadeesh B, Laxmi KN, Laxmi PR, Reddy PR, Mullangi R. Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of zafirlukast, a selective leukotriene antagonist in human plasma: application to a clinical pharmacokinetic study. Biomed. Chromatogr. 22: 645-653, 2008.

External links[edit]