Aspira Mechanism of Action

Pharmacology: Pharmacodynamics: Montelukast is a selective and active leukotriene receptor antagonist. Montelukast inhibits bronchoconstriction due to antigen challenge. Montelukast is a selective leukotriene receptor antagonist of the cysteinyl leukotriene CysLT1 receptor. The cysteinyl leukotrienes (LTC 4, LTD 4, LTE 4) are products of arachidonic acid metabolism that are released from various cells, including mast cells and eosinophils. They bind to cysteinyl leukotriene receptors (CysLT) found in the human airway. Binding of cysteinyl leukotrienes to leukotriene receptors has been correlated with the pathophysiology of asthma, including airway edema, smooth muscle contraction and altered cellular activity associated with the inflammatory process, factors that contribute to the signs and symptoms of asthma.
It binds to CysLT type-1 receptors found in human airway (smooth muscle cells and macrophages), which prevents airway edema, smooth muscle contraction and other respiratory inflammation. The leukotrienes are also released from the nasal mucosa after allergen exposure where montelukast sodium may inhibit symptoms of allergic rhinitis.
Montelukast binding to the CysLT1 receptor is high-affinity and selective, preferring the CysLT1 receptor to other pharmacologically important airway receptors eg, the prostanoid, cholinergic or β-adrenergic receptor. Montelukast inhibits physiologic actions of LTD4 at the CysLT1 receptors, without any agonist activity.
Montelukast causes bronchodilation within 2 hrs of oral administration; these effects were additive to the bronchodilation caused by a β-agonist.
Pharmacokinetics: Absorption: Montelukast is rapidly and nearly completely absorbed following oral administration. Peak plasma concentrations of montelukast occur 3-4 hrs after oral doses. The mean oral bioavailability is 64%. The oral bioavailability and peak plasma concentration (C_max) are not influenced by a standard meal.
Distribution: Montelukast is >99% bound to plasma proteins. The steady-state volume of distribution of montelukast averages 8-11 L. Studies in rats with radiolabeled montelukast indicate minimal distribution across the blood-brain barrier.
Metabolism: Montelukast is extensively metabolized in the liver by cytochrome P-450 isoenzymes CYP3A4 and CYP2C9. Therapeutic plasma concentrations of montelukast do not inhibit cytochromes P-450 3A4, 2C9, 1A2, 2A6, 2C19 or 2D6.
Elimination: The plasma clearance of montelukast averages 45 mL/min in healthy adults. Montelukast and its metabolites are excreted principally in the faeces via the bile.
Elimination Half-Life: 2.7-5 hrs.