Saltrol Mechanism of Action

Pharmacology: Pharmacodynamics: Salmeterol: Salmeterol is a selective long-acting (12 hour) β₂ adrenoceptor agonist with a long side chain which binds to the exo-site of the receptor. The pharmacologic effects of β₂ adrenoceptor agonist drugs, including salmeterol, are at least in 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 cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.
Fluticasone propionate: Fluticasone propionate given by inhalation at recommended doses has a glucocorticoid anti-inflammatory action within the lungs, resulting in reduced symptoms and exacerbations of asthma, with less adverse effects than when corticosteroids are administered systemically.
Pharmacokinetics: Salmeterol: Salmeterol acts locally in the lung therefore plasma levels are not an indication of therapeutic effects. The percentage of salmeterol bound to human plasma proteins averages 96% in vitro over the concentration range of 8 to 7,722ng of salmeterol base per milliliter. Salmeterol is extensively metabolized by hydroxylation, with subsequent elimination predominantly in the feces. No significant amount of unchanged salmeterol base was detected in either urine or feces.
Fluticasone propionate: Fluticasone propionate acts locally in the lung therefore plasma levels do not predict therapeutic effects. Oral systemic bioavailability of Fluticasone propionate is negligible (less than 1%) primarily due to incomplete absorption and presystemic metabolism in the gut and liver. The disposition of Fluticasone propionate is characterized by high plasma clearance (1150mL/min), a large volume of distribution at steady-state (approximately 300L) and a terminal half-life of approximately 8 hours. Plasma protein binding is 91%. Fluticasone propionate is cleared very rapidly from the systemic circulation. The main pathway is metabolism to an inactive carboxylic acid metabolite, by the cytochrome P450 enzyme CYP3A4. Other unidentified metabolites are also found in the feces. The renal clearance of Fluticasone propionate is negligible. Less than 5% of the dose is excreted in urine, mainly as metabolites. The main part of the dose is excreted in feces as metabolites and unchanged drug.