Duramont Mechanism of Action

Pharmacology: Montelukast sodium is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene CysLT receptor.
Mechanism of Action: 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 cysteinyl leukotriene (CysLT) receptors. The CysLT type-1 (CysLT1) receptor is found in the human airway (including airway smooth muscle cells and airway macrophages) and on other pro-inflammatory cells (including eosinophils and certain myeloid stem cells). CysLTs have been correlated with the pathophysiology of asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include airway edema, smooth muscle contraction and altered cellular activity associated with the inflammatory process.
In allergic rhinitis, CysLTs are released from the nasal mucosa after allergen exposure during both early- and late-phase reactions and are associated with symptoms of allergic rhinitis. Intranasal challenge with CysLTs has been shown to increase nasal airway resistance and symptoms of nasal obstruction.
Montelukast is an orally active compound that binds with high affinity and selectivity to the CysLT1 receptor (in preference to other pharmacologically important airway receptors eg, prostanoid, cholinergic or β-adrenergic receptor). Montelukast inhibits physiologic actions of LTD4 at the CysLT1 receptor without any agonist activity.
Pharmacokinetics:  Montelukast is rapidly absorbed following oral administration. After administration of the 10-mg tablet, the mean peak montelukast plasma concentration (C_max) is achieved in 3-4 hrs (T_max). The mean oral bioavailability is 64%. 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. In addition, concentrations of radiolabeled material at 24 hrs post-dose were minimal in all other tissues. Montelukast is extensively metabolized. In vitro studies using human liver microsomes indicate that cytochromes P-450 3A4 and 2C9 are involved in the metabolism of montelukast.
The plasma clearance of montelukast averaged 45 mL/min in healthy adults. Montelukast and its metabolite are excreted almost exclusively via the bile. In several studies, the mean plasma half-life (t_½) of montelukast ranged from 2.7-5.5 hrs in healthy young adults.
The pharmacokinetics of montelukast are similar in males and females. The pharmacokinetic profile and the oral bioavailability of a single 10-mg oral dose of montelukast are similar in elderly and younger adults. The plasma t_½ of montelukast is slightly longer in the elderly. No dosage adjustment in the elderly is required.
Hepatic Insufficiency: No dosage adjustment is required in patients with mild to moderate hepatic insufficiency. The pharmacokinetics of montelukast in patients with more severe hepatic impairment or with hepatitis have not been evaluated.
Renal Insufficiency: Since montelukast and its metabolites are not excreted in the urine, the pharmacokinetics of montelukast have not been evaluated in patients with renal insufficiency. No dosage adjustment is recommended in these patients.