with a severe asthma phenotype, has been shown to decrease the clinical response to zafirlukast (both when the genetic alteration was heterozygous or homozygous). CYP2C9 Zafirlukast is metabolized through the hepatic enzyme CYP2C9. SNPs that decrease the function of CYP2C9 (such as CYP2C9*3 and CYP2C9*13) may decrease the hepatic clearance of zafirlukast, leading to increased exposure of zafirlukast. Notably, the CYP2C9*3 polymorphism is more commonly encountered in people of south/central Asian ancestry (10.165%) compared to people of Caucasian (7.083%), African American (1.170%), African (1.033%), middle eastern (9.312%), and east Asian (3.365%) ancestry. Chemistry Synthesis Zafirlukast can be synthesized by the following method: Physiochemical properties Pure zafirlukast is described as a fine, white to pale yellow, amorphous powder. It is practically insoluble in water, slightly soluble in methanol, and freely soluble in tetrahydrofuran, dimethylsulfoxide, and acetone. History Zafirlukast was the first cysteinyl leukotriene receptor antagonist approved in the United States. Zafirlukast was approved in 1996. Society and culture Economics While preliminary evidence suggests that zafirlukast may reduce healthcare costs, the cost-effectiveness of using zafirlukast has not been established. Brand names Research Mechanism of action There is some research to suggest that zafirlukast actually acts as a partial inverse agonist at the CysLT1 receptor, though zafirlukast is still classified as an antagonist at this receptor. The possible clinical significance of this effect, if true, is unknown. Other indications There is some evidence that suggests that zafirlukast may be beneficial in the treatment of chronic urticaria (hives), whether due to a known cause such as cold-exposure or due to an unknown cause (idiopathic). A pilot study indicated that zafirlukast may be of some benefit in cystic fibrosis. In the setting of chronic obstructive pulmonary disorder (COPD), a disease characterized by chronic inflammation of the lungs, zafirlukast has been shown to improve lung function. Veterinary use Zafirlukast is sometimes used for the treatment of bronchial asthma in cats. References External links Leukotriene antagonists Carbamates Indoles AstraZeneca brands Phenol ethers Sulfonamides Cyclopentanes