Based on data from the manufacturer, it is expected that 0.6% of the maternal weight-adjusted dose would reach a breastfed infant, though the effects in the infant are unknown. Renal impairment
Renal impairment does not appear to affect the pharmacokinetic profile of zafirlukast. Hepatic impairment
The hepatic clearance of zafirlukast is impaired by significant hepatic impairment. Cirrhosis of the liver can result in an increase in the maximum plasma concentration and the total area under the curve (a measure of drug exposure) by 50–60%. Contraindications
Zafirlukast is contraindicated in people that are hypersensitive or allergic to it. Adverse effects
Zafirlukast is generally well tolerated, though headache and gastrointestinal (GI) upset can occur. The incidence of headache is between 12 and 20%, which is similar to the incidence of headache found in patients taking placebos in the studies that lead to zafirlukasts approval. GI upset may include nausea, stomach discomfort/pain, and diarrhea. GI complaints can be lessened by taking zafirlukast with food, though this can dramatically impair the amount of drug that gets absorbed into the body (see the section on drug-food interactions below).Other common side effects include flu-like symptoms, sleep disturbances (abnormal dreams, insomnia), hallucinations, and daytime drowsiness. Neuropsychiatric effects
Neuropsychiatric side effects have been reported with the use of zafirlukast and other LTRAs. While some side effects are less severe (e.g. abnormal dreams), others are more serious (e.g. hallucinations, tremor, suicidality). These effects were discovered through post-marketing reports, as the initial trials were not designed to monitor for neuropsychiatric side effects.
Albumin is the most abundant protein found in human plasma and is capable of carrying and transporting drugs (like zafirlukast) throughout the body. In vivo research indicates that zafirlukast has low blood-brain barrier penetration. The blood-brain barrier is a protective system that prevents many chemicals from entering the brain. Metabolism
Zafirlukast undergoes extensive hepatic metabolism into inactive metabolites. Zafirlukast is primarily metabolized by the enzyme CYP2C9 to a hydroxylated metabolite. Elimination
Zafirlukast is primarily cleared through biliary excretion at a rate of 20 liters/hour. Zafirlukast is undetectable in urine. The mean terminal half-life ranges 8–16 hours, following linear kinetics up to doses of 80 mg.

Pharmacogenomics
LTC4 synthase
Genetic polymorphisms in the LTC4 synthase promoter may predict response to zafirlukast. The single-nucleotide polymorphism (SNP) A444C (the wild-type DNA base adenine, at the 444th position on the gene, is mutated; cytosine is there instead), which is associated 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.