Salmeflo Mechanism of Action

Pharmacology: The combination represent 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.
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).
Salmeterol Xinafoate: It is a long-acting beta2-adrenergic agonist. The pharmacologic effect of Salmeterol Xinafoate is part attributable to stimulation of intracellular adenyl 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 shows 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.
Mechanism of Action: Salmeterol and Fluticasone propionate have different mode of action. Salmeterol protects against symptoms. Fluticasone propionate improves lung function and prevent exacerbations. Salmeterol + Fluticasone propionate can offer a more convenient regimen for patients on concurrent β-agonist and inhaled corticosteroid therapy.
Pharmacokinetics: There is no evidence in animal or human subjects that the administration of Salmeterol and Fluticasone propionate together by the inhaled route affects the pharmacokinetics of either component. For pharmacokinetic purposes, therefore each component can be considered separately. Even though plasma levels of Salmeterol + Fluticasone are very low. Potential interactions with other substrates and inhibitors of CYP 3A4 cannot be excluded. Salmeterol acts locally in the lungs 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 in the drug due to the low plasma concentrations at the therapeutic doses (approximately 200 mg/mL or less) achieved after inhaled dosing. After regular dosing with salmeterol xinafoate, hydroxynaphthoic acid can be detected in the systemic circulation, reaching steady state concentrations of approximately 100 mg/mL, these concentrations are up to 1000 fold lower than the steady state levels observed in toxicity studies. In toxicity studies no detrimental effects have been seen following long term regular dosing (more than 12 months) in patients with airways obstruction.