Drug Groups

approved; investigational

Description

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), which is usually taken just once daily.

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.

Indication

For the prophylaxis and chronic treatment of asthma.

Pharmacology

Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA) 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.

Toxicity

Side effects include rash and upset stomach.

Affected Organisms

Biotransformation

Hepatic

Absorption

Rapidly absorbed following oral administration, reduced following a high-fat or high-protein meal.

Half Life

10 hours

Protein Binding

99%

Elimination

The most common metabolic products are hydroxylated metabolites which are excreted in the feces.

Distribution

* 70 L

Clearance

* apparent oral cl=20 L/h
* 11.4 L/h [7-11 yrs]
* 9.2 L/h [5-6 yrs]

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