almeterol xinafoate is a white powder with a molecular weight of 603.8, and the empiricalformula is C25H37NO4•C11H8O3. It is freely soluble in methanol; slightly soluble in ethanol,chloroform, and isopropanol; and sparingly soluble in water.
AirDuo DigihalerAirDuo Digihaler is a multidose dry powder inhaler (MDPI) with an electronic module, for oralinhalation only. It contains fluticasone propionate, salmeterol xinafoate, and lactosemonohydrate (which may contain milk proteins). The opening of the mouthpiece cover meters5.5 mg of the formulation from the device reservoir, which contains 55 mcg, 113 mcg, or 232mcg of fluticasone propionate, and 14 mcg of salmeterol base (equivalent to 20.3 mcg ofsalmeterol xinafoate). Patient inhalation through the mouthpiece causes the deagglomeration andaerosolization of the drug particles as the formulation moves through the cyclone component of
the device. This is followed by dispersion into the airstream.
Under standardized in vitro test conditions, the AirDuo Digihaler inhaler delivers 49 mcg, 100mcg, or 202 mcg of fluticasone propionate and 12.75 mcg of salmeterol base (equivalent to 18.5mcg of salmeterol xinafoate), with lactose from the mouthpiece when tested at a flow rate of 85L/min for 1.4 seconds.
The amount of drug delivered to the lung will depend on patient factors such as inspiratory flowprofiles. In adult subjects (N=50, aged 18 to 45 years) with asthma, mean peak inspiratory flow(PIF) through the MDPI was 108.28 L/min (range: 70.37 to 129.24 L/min). In adolescentsubjects (N=50, aged 12 to 17 years) with asthma, mean peak inspiratory flow (PIF) through theMDPI was 106.72 L/min (range: 73.64 to 125.51 L/min).
AirDuo Digihaler includes a QR code (on the top of the inhaler), and contains a built-inelectronic module which automatically detects, records and stores data on inhaler events,including peak inspiratory flow rate (L/min). AirDuo Digihaler may pair with and transmit datato the mobile App where inhaler events are categorized.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
AirDuo Digihaler: AirDuo Digihaler contains both fluticasone propionate and salmeterol. Themechanisms of action described below for the individual components apply to AirDuo Digihaler.
These drugs represent 2 different classes of medications (a synthetic corticosteroid and a LABA)that have different effects on clinical, physiologic, and inflammatory indices.
Fluticasone Propionate: Fluticasone propionate is a synthetic trifluorinated corticosteroid withanti-inflammatory activity. Fluticasone propionate has been shown in vitro to exhibit a bindingaffinity for the human glucocorticoid receptor that is 18 times that of dexamethasone, almosttwice that of beclomethasone-17-monopropionate (BMP), the active metabolite ofbeclomethasone dipropionate, and over 3 times that of budesonide. Data from the McKenzievasoconstrictor assay in humans are consistent with these results. The clinical significance ofthese findings is unknown.
Inflammation is an important component in the pathogenesis of asthma. Corticosteroids havebeen shown to have a wide range of actions on multiple cell types (e.g., mast cells, eosinophils,neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids,leukotrienes, and cytokines) involved in inflammation. These anti-inflammatory actions ofcorticosteroids contribute to their efficacy in the treatment of asthma.
S |
