Muloz Mechanism of Action

Pharmacology:Pharmacodynamics: Montelukast sodium is a selective and competitive leukotriene receptor antagonist that affects inflammatory processes involved in asthma and allergic rhinitis. Montelukast is a selective leukotriene receptor antagonist of the cysteinyl leukotriene (CysLT) receptor.
The cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. These eicosanoids bind to CysLT receptors. Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of allergic rhinitis and asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process. The CysLT type 1 (CysLT₁) receptor is found in the human airway (including airway smooth muscle cells and airway macrophages) and on other proinflammatory cells (including eosinophils and certain myeloid stem cells). Montelukast binding to the CysLT₁ receptor is high-affinity and selective, preferring the CysLT₁ receptor to other pharmacologically important airway receptors, such as the prostanoid, cholinergic, or beta-adrenergic receptor. Montelukast inhibits physiologic actions of LTD₄ at the CysLT₁ receptor, without any agonist activity.
Pharmacokinetics: Absorption: Montelukast is rapidly absorbed from the GI tract. For the 5 mg chewable tablet, the C_max is achieved in 2 hours after administration in adults in the fasted state. The mean oral bioavailability in adults is 73%.
Distribution: Montelukast is more than 99% bound to plasma proteins. The steady-state volume of distribution of Montelukast is 8-11 L.
Metabolism: Montelukast is extensively metabolized in the liver by cytochrome P450 isoenzymes, mainly by CYP2C8 and to a lesser extent by CYP3A4 and CYP2C9.
Excretion: The mean plasma half-life of Montelukast is 2.7-5.5 hours. The plasma clearance of Montelukast averages 45 mL/min. Following an oral dose of radiolabeled Montelukast, 86% of the radioactivity was recovered feces and <0.2% was recovered in urine. Montelukast is excreted principally in bile as unchanged drug and metabolites.