Forair 250 DPI/Forair 500 DPI

Forair 250 DPI/Forair 500 DPI Mechanism of Action

salmeterol + fluticasone


Zydus Healthcare


Zydus Healthcare
Full Prescribing Info
Pharmacology: Pharmacodynamics: The combination represents 2 classes of medications (a synthetic corticosteroid and a selective, long-acting beta-adrenergic receptor agonist) that have different effects on clinical and physiological indices.
Salmeterol xinafoate: It is a long acting beta-2-adrenergic agonist. The pharmacologic effect of Salmeterol Xinafoate is part attributable to stimulation of intracellular adenylyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels caused relaxation of bronchial smooth muscle and inhibition of release mediators of immediate hypersensitivity from cells, especially from mast cells. In vitro tests show that salmeterol is a potent and long-lasting inhibitor of the release of mast cell mediator, such as histamine. leukotrienes and prostaglandin D2, from human lung. Salmeterol inhibits histamine-induced plasma protein extravasation and inhibits platelet-activating factor-induced eosinophil accumulation in the lungs of guinea pigs when administered by the inhaled route.
Fluticasone propionate: It is a synthetic trifluorinated corticosteroid with potent anti-inflammatory activity. In vitro assays using human lung cytosol preparations have established fluticasone propionate as a human glucocorticosteroid receptor agonist with an affinity 18 times greater than dexamethasone, almost twice that of beclomethasone-17-monopropionate (BMP), the active metabolite of beclomethasone dipropionate and over 3 times that of budesonide. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to inhibit multiple cell types (e.g. mast cells, eosinophils. basophils, lymphocytes. macrophages and neutrophils) and mediator production or secretion (e.g. histamine, eicosanoids. leukotrienes and cytokines) involved in the asthmatic response. These anti-inflammatory actions of corticosteroids contribute to their efficacy in asthma. Inflammation is also a component in the pathogenesis of chronic obstructive pulmonary disease (COPD).
Pharmacokinetics: Salmeterol xinafoate: Salmeterol acts locally in the lung therefore plasma levels are not an indication of therapeutic effects. In addition, there are only limited data available on the pharmacokinetics of salmeterol because of the technical difficulty of assaying the drug in plasma due to the low plasma concentrations at therapeutic doses (approximately 200 picograms/mL or less) achieved after inhaled dosing.
After regular dosing with salmeterol xinafoate, hydroxynapthoic acid can be detected in the systemic circulation, reaching steady state concentrations of approximately 100 nanograms/mL.
These concentrations are up to 1000 fold lower than steady state levels observed in toxicity studies. No detrimental effects have been seen following long-term regular dosing (more than 12 months) in patients with airway obstruction.
Fluticasone propionate: Systemic absorption occurs mainly through the lungs and is initially rapid than prolonged. The remainder of the inhaled dose may be swallowed but contributes minimally to systemic exposure due to the low aqueous solubility and pre-systemic metabolism, resulting in oral bioavailability of less than 1%. There is a linear increase in systemic exposure with increasing inhaled dose. The disposition of fluticasone propionate is characterized by high plasma clearance (1150 mL/min), a large volume of distribution at steady state (approximately 300L) and a terminal half-life of approximately 8 hours. Plasma protein binding is moderately high (91%). Fluticasone propionate is cleared very rapidly from the systemic circulation, principally by metabolism to an inactive carboxylic acid metabolite, by the cytochrome P450 enzyme CYP3A4. The renal clearance of fluticasone propionate is negligible (<0.2%) and less than 5% as the metabolite. Care should be taken when co-administering known CYP3A4 inhibitors. as there is potential for increased systemic exposure to fluticasone propionate.
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