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Pharmacology: Pharmacodynamics: Montelukast is a selective leukotriene-receptor antagonist that specifically inhibits the cysteinyl leukotriene CysLT1 receptor. The cysteinyl leukotrienes [CysLT (LTC4, LTD4, and LTE4)] are potent inflammatory eicosanoids released from various cells including mast cells and eosinophils that bind to CysLT receptors. The CysLT type 1 (CysLT1) receptor is present in the human airway (including airway smooth muscle cells and airway macrophages). CysLTs contribute to the pathophysiology of asthma and allergic rhinitis. In asthma, CysLTs are found to increase mucus secretion, vascular permeability, and bronchoconstriction. In allergic rhinitis, CysLTs are released from the nasal mucosa after exposure to allergens and are associated with symptoms of allergic rhinitis. Montelukast inhibits bronchoconstriction and reduces inflammation of the nasal mucosa induced by exposure to known precipitants.
Pharmacokinetics: Montelukast is rapidly absorbed after oral administration. After administration of 10 mg film-coated tablet in adults in the fasted state, mean peak montelukast plasma concentration (Cmax) is achieved in 3 to 4 hours. The mean oral bioavailability is 64%. The oral bioavailability and Cmax are not influenced by a standard meal in the morning.
In two pharmacokinetic trials in asthmatic pediatric patients aged 2 to 5 years and 6 to 14 years, peak plasma concentrations of montelukast 4 mg (471 ± 65 ng/mL) and 5 mg (495 ± 129 ng/mL) as chewable tablets are attained within 2.07 ± 0.3 hours and 2.6 ± 1 hours, respectively.
In a pharmacokinetic trial in asthmatic pediatric patients 6 to 24 months old, peak plasma concentrations (514.4 ng/mL) of montelukast 4 mg as oral granules are attained within 2.2 hours.
Montelukast's steady state volume of distribution is 8 to 11 liters. Plasma protein binding is more than 99%.
Montelukast is extensively metabolized in the liver by cytochrome P450 isoenzymes CYP2C8, CYP3A4, and CYP2C9, and is excreted principally in the feces via the bile.
